EMjournal Vol3N1 RS - PeaceHealth...Southwest Regional Cancer Center • 2010 Annual Report Incidence T he risk of a woman developing breast cancer, invasive and ductal carcinoma in

Exceptional MedicineSouthwest Physicians Journal • Volume 3, Number 1, Fall 2010

“Early detection is probably the single most important aspect in the management of breast cancer that we can impact.”

—- Toni Storm-Dickerson, MD, FACSSouthwest Regional Cancer Center

MANAGEMENT

Winning the Breast Cancer Battle: Early Detection and Improved Treatments Can Save Lives

See page 1

RISK

Hereditary Breast Cancer: Identifying and Managing Risk of Inherited Breast Cancer Syndrome

See page 24

DETECTION AND

STAGING

Introduction to Breast MRI

See page 28

THERAPY

Radiation Therapy for Breast Cancer: Emerging Options Demonstrate the Value of Less Treatment

See page 30

2010 ANNUAL REPORT

ExceptionalMedicine

Southwest Physicians Journal Fall 2010Volume 3, Number 1

PUBLISHING STAFF

Editorial Director

Kenneth Cole

Assistant Managing Editor

Sarah Mottram

Contributing Editors

Alden Roberts, MD

Brian Harwood, MD

Chris O’Hara, RN

Submission Guidelines

Exceptional Medicine is a free,

editorial-reviewed publication

by credentialed Medical Center

staff for regional physicians.

For complete details and

submission guidelines, go to

www.swmedicalcenter.org/

exceptionalmedicine

or contact the editorial staff

([email protected] or

360.514.3066).

Mission StatementAs the leader in the provision of health services for our entire community, we emphasize clinical and service quality, promote accessible and affordable care and work with others to improve health status.

© Copyright 2010 Southwest Washington Medical Center, Marketing Department, PO Box 1600, Vancouver, WA 98668

www.swmedicalcenter.org/ exceptionalmedicine

TABLE OF CONTENTS

Management


Toni Storm-Dickerson, MD, FACS; Mohiedean Ghofrani, MD; Clifford S. Pukel, MD; S. Chris Hoffelt, MD; Michael Morich, MD; Becky Hambright, RN, OCN, CCRP; Marie Tesdale, RHIT, CTR cancer registrar; Southwest Regional Cancer Center; Southwest Washington Medical Center, Vancouver, WA

Early detection is probably the single most important aspect in the management of breast cancer that we can impact. Early detection results in discovering lower stage cancers which directly translates into higher survival rates. Survival is inversely proportional to stage, thus illustrating the importance of early detection by means of self exam, practitioner clinical exam and imaging.

Risk

Hereditary Breast Cancer: Identifying and Managing Risk of Inherited Breast Cancer Syndromes

Michaelann L. Liss, DO

The hallmarks of hereditary breast cancers are young age at diagnosis and in most cases, a family history consistent with multiple affected family members in multiple generations. Once high-risk individuals are identifi ed, genetic counseling and risk assessment can be offered and when indicated, gene sequencing can be done to identify genetic mutations.

Detection and Staging

Introduction to Breast MRI

Michael Morich, MD

Contrast enhanced breast MRI is now widely used at most breast imaging centers. It has shown to be extremely sensitive in the detection of breast cancer. However, increased sensitivity of breast MRI also leads to unnecessary follow-up and biopsies. Breast MRI must be utilized carefully and in the appropriate patient population for optimal results.

Therapy

Radiation Therapy for Breast Cancer: Emerging Options Demonstrate the Value of Less Treatment

S. Christopher Hoffelt, MD

Radiation therapy has played an important role in the treatment of breast cancer for decades. Technology and well-designed prospective studies, most in the past ten years, have had a major impact on the way radiation therapy is given and changed the role of radiation as a component of treatment for breast cancer in curable stages.

1Volume 3, Number 1 Exceptional Medicine

Southw

est Reg

ional C

ancer Center • 2010 A

nnual Rep

ort

Incidence

The risk of a woman developing breast cancer, invasive and ductal carcinoma in situ (DCIS), in her lifetime is currently estimated at 14.1% or 1 in 6, (1 in 8 for invasive disease only) per Jermal et al.1 Breast cancer is the most common cancer in women other than skin cancer, the number 2 cause of cancer deaths in women, and the main cause of cancer death in women ages 40 to 59. Breast cancer is rare in men, accounting for approximately 1% of the total cases. In the US approximately 182,460 women are diagnosed with breast cancer annually, and more than 40,000 will die from the disease.2

Although incidence of breast cancer is signifi cantly higher in women age 50 and older (375 per 100,000) compared with women younger than 50 (42.5 per 100,000) approximately 23% of breast cancers are diagnosed in women under the age of 50.3 Of those cases seen at Southwest Washington Medical Center, 19% occurred in women under 50 years of age.

(Refer to Table 1: Estimated Cancer Deaths from Breast Cancer – 2009; Table 2: Estimated Cancer Deaths from Breast Cancer – 2010)

Since 1975, breast cancer mortality rates have declined by about 37%.1 The most important factor in improving survival is early detection.

Early detection is probably the single most important aspect in the management of breast cancer that we can impact. Early detection results in discovering lower stage cancers which directly translates into higher survival rates. Survival is inversely proportional to stage, thus illustrating the importance of early detection by means of self exam, practitioner clinical exam and imaging.

In this paper, we examine several facets of breast cancer including risk factors, early detection, cancer type, staging and treatment.

Correspondence:

Toni Storm-Dickerson, MDtstorm@pacifi csurg.com

Southwest Washington Medical Center Regional Cancer CenterPO Box 1600Vancouver, WA 98668360.514.2174www.swmedicalcenter.org/cancercenter

Department of General Surgery Southwest Washington Medical Center505 NE 87th Avenue, Suite 301Vancouver, WA 98664360.514.7374


Toni Storm-Dickerson, MD, FACS; Mohiedean Ghofrani, MD; Clifford S. Pukel, MD; S. Chris Hoffelt, MD; Michael Morich, MD; Becky Hambright, RN, OCN, CCRP

Southwest Regional Cancer Center, Southwest Washington Medical Center, Vancouver, WA

Table 1: Estimated Cancer Deaths from Breast Cancer – 2009In 2009, breast cancer deaths in Washington State accounted for nearly 2% of the nationwide total.

• Washington State – 790• United States - 40,170 *Data from ACS Cancer Facts and Figures 2009

Table 2: Estimated Cancer Deaths from Breast Cancer – 2010According to the National Cancer Institute, the annual number of deaths from breast cancer is relatively consistent, hovering at around 40,000 per year. .

• United States – 39,840*Data from National Cancer Institute, Surveillance Epidemiology and End Results.

2 Fall 2010www.swmedicalcenter.org

Figure 1: Age at Breast Cancer Diagnosis – Southwest 200956% of women diagnosed with breast cancer at Southwest in 2009 were between the ages of 50-69.

45

40

35

30

25

20

15

10

5

0Age 0-29 Age 30-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Age 80-89 Age 90+

Stage 0

Stage 1

Stage 2

Stage 3

Stage 4

Unknown1 1

5

24

2 2 2 21

1011 12

20 20

13

3 34

89

7

1 1

4143

2523

1416

15

1

50

Figure 2: Age at Breast Cancer Diagnosis by Stage – Southwest 2009The majority of women in each age category from 40-89 were diagnosed with Stage 1 breast cancer.

Age 50 – 59

Age 60 – 69

Age 70 – 79

Age 0 – 29

Age 30 – 39

Age 40 – 49

Age 80 – 89

Age 90+

14%

1%4%1%

28%

28%

16%

8%


(See Figure 1: Age at Breast Cancer Diagnosis – Southwest 2009)

Globally, this is a very different picture with the inci-dence of breast cancer in Africa and Asia ranging at ap-proximately 30-40% of that seen in the US, with mortal-ity rates nearly equal to the US and the Western world.4 Breast cancer mortality rates have actually declined since 1975 by about 37%.1 The most important factor in improving survival is early detection, and this improve-ment is attributed to the increased use of screening mammography. In the early 1980s, breast cancer inci-dence actually increased by 3.7% per year, coinciding with increase in the diagnosis of DCIS and early stage breast cancers. Thus, mammography’s ability to identify previously undetectable early breast cancers caused an artifi cial increase in the incidence of breast cancer. These studies support the assumption that increased screen mammograms translate into lives saved through early diagnosis and treatment and thus decreased mortality.

Since 1987 the incidence of breast cancer has primar-ily leveled off, although there was an 8.6% decrease incidence in 2002-2003 seen in women 50 and over in ER+ rather than ER- cancer. This was thought to be secondary to the drop in hormone replacement in post-menopausal women.5

Risk Factors

Approximately half of the time we can identify known risk factors, such as age at menarche, fi rst live birth, menopause, and proliferative breast disease or family history (approximately 10% of cases are linked to a posi-tive family history). That leaves 50% of breast cancers striking indiscriminately.

Gender and Age

Gender and age are the clearly among the strongest of the risk factors. Breast cancer is 100 times more likely in women than men and increases with age. Breast can-cer is rare in women under 20 although there are case reports of breast cancer as young as 14, and cases under the age of 30 constitute less than 2% of total breast can-cers. The incidence increases to 1 in 93 by age 40, 1 in 50 by age 50, 1 in 24 by age 60, and 1 in 14 by age 70 (these statistics do not include DCIS).6

(See Figure 2: Age at Breast Cancer Diagnosis by Stage)

Family History and Genetic Risk Factors

Please see Hereditary Breast Cancer: Identifying and Managing Risk of Inherited Breast Cancer Syndromes by Michaelann Liss, MD, included in this edition of the Exceptional Medicine Journal.

Race, Ethnicity, Geography

In the US, breast cancer is the most common cancer (excluding skin cancer) among all women, regardless of ethnic group. However, there are some surprising differ-ences between racial groups and geographic location. Whites have the highest incidence at 133 per 100,000 (in Washington state 143 per 100,000), blacks are slightly lower at 118 per 100,000 (Washington state 111.4 per 100,000) and Native Americans and Alaskans are lowest at 70 per 100,000.7 However, in spite of the lower overall incidence, of breast cancer in African American women, 24.3 per 100,000, the mortality rate is higher at 29.7 per 100,000. This is likely due to both more advanced stage at diagnosis and higher stage-specifi c mortality in Afri-can American women. Some data suggest that African American women have more aggressive cancers (e.g., hormone receptor-negative) that are associated with a higher mortality rate.8

Benign Breast Disease

Benign breast fi ndings categorized as proliferative lesions or those without Atypia, would include benign entities such as fi brocystic breast disease, papilloma, fi broadenoma, sclerosing adenosis, and radial scar. These are not generally associated with an increased risk for breast cancer, although relative risk is increased 1.3 to 2.9

Proliferative lesions with atypia are considered to be potential precursors to invasive breast disease. These include LIN 2 and 3 and DIN 1 (atypical lobular hyper-plasia, atypical ductal hyperplasia) with a higher relative risk 4 to 6. This is increased to 10-fold when the atypia is multifocal.9

Lobular Carcinoma In Situ and Personal History of Breast Cancer

Lobular Carcinoma In Situ (LCIS) is a changing term, as is much in breast cancer these days. For the purpose of risk factor assessment in this paper, we are referring to Low to Intermediate grade LCIS only (LIN 1, 2). LCIS is a noninvasive lesion arising in the breast lobules and terminal ducts. It is a less common diagnosis and is seen predominantly in younger, premenopausal, women.


350

300

250

200

150

100

50

02008

Year20092000 2001 2002 2003 2004 2005 2006 2007

212

Num

ber

of

Cas

es 260 255274

238265 254 265

313 322Figure 3: Ten-year Breast Cancer Incidence – Southwest The number of breast cancer cases at Southwest reached a 10-year high in 2009.

Figure 4: Stage at Breast Cancer Diagnosis – SouthwestApproximately 42% of all breast cancers seen at Southwest in 2009 were Stage 1.

Generally it does not form a palpable mass, is not seen as calcifi cation on mammography and is usually found serendipitously on biopsy for another fi nding. LIN 1 and 2 are not considered precursors to invasive disease but rather a marker for an increased risk of bilateral breast cancer. Haagensen collected the largest series of pa-tients with LCIS. He looked at more than 5,000 biopsies performed for benign disease and found LCIS in 3.6%.10 He then followed these patients closely over 35 years and found that the actuarial probability of carcinoma developing was 21.4%, of which 40% were in situ le-sions. Of the invasive cancers that developed, they were predominantly ductal not lobular and half occurred on the contralateral breast.

Thus, a history of LCIS increases the risk of both invasive ductal and invasive lobular carcinoma. LCIS is also fre-quently multifocal and bilateral, which is not surprising when considering it as a risk factor for bilateral disease. In the presence of LCIS, the risk for invasive breast can-cer is 1% per year in both breasts regardless of the site of original diagnosis.11

Management recommendation should include close sur-veillance with annual to biannual breast exam, monthly self exams and annual mammograms. This is in agree-ment with the National Comprehensive Cancer Network (NCCN) guidelines. We would also recommend assess-ment by an oncologist for possible chemo prevention to be determined on an individual basis.

140

160

120

100

80

60

40

20

0Unk/NAStage II Stage III Stage IV

58

138

92

2111

2


(See Figure 3: Ten-year Breast Cancer Incidence – Southwest; Figure 4: Stage at Breast Cancer Diagnosis – Southwest)

Personal History of Invasive or In Situ Breast Cancer (includes DCIS and high grade LCIS)

A personal history of breast cancer increases the risk of developing an invasive breast cancer in the contralateral breast. With in situ lesions, the 10-year risk of devel-oping a contralateral invasive breast cancer is 5%.12 In women with invasive breast cancer, the risk of develop-ing contralateral breast cancer is 1 and 0.5 percent per year for premenopausal and postmenopausal women, respectively.

Alcohol and Dietary Factors

This is a very extensive area of both debate and re-search. For the purposes of this report we will briefl y review these. Moderate to high alcohol consumption (more than 3 drinks/day) has been consistently shown to increase risk for receptor positive breast cancers.13 Folate has been found to be inversely related (protec-tive) to breast cancer especially in younger women who consume alcohol.14

The Nurses’ Health Study15 showed an additive affect of postmenopausal hormone replacement and alcohol on increasing breast cancer risk (approximately 1.3 fold). Theorized explanations for this phenomenon include increased circulating estrogen and androgens, enhanced mammary gland susceptibility to carcinogens, DNA damage or increased invasive potential of the individual breast cancer cells.16 The role of fat intake, on the other hand, is less clear but is often associated with obesity which is associated with an increase risk for all cancers. However, while early studies showing high fat diets increasing the occurrence of mammary tumors in mice, more recent studies have not been able to confi rm this observation.17,18,19

Weight and Obesity

Weight and body mass index (BMI) have opposite infl u-ences on postmenopausal as compared to premeno-pausal breast cancer. In postmenopausal breast cancer higher weight/BMI and postmenopausal weight gain have been associated with a higher risk of breast cancer in multiple studies.20,21,22 This is thought to be a result of higher circulating levels of estrogens from increased conversion of adipose (fat) tissue estrogen precursors to estrogen. The Nurses’ Health Study showed that, in postmenopausal women, mean serum estradiol levels

were signifi cantly higher among women with a BMI ≥29 kg/m2 compared to those with a BMI


increased risk for breast cancer. While no single study has been able to clearly prove a relationship between OCP and breast cancer, a pooled analysis of 54 epidemi-ologic studies on 53,297 women with breast cancer and 100,239 women without breast cancer calculated a small increase in the relative risk of breast cancer (RR=1.24) in women who use oral contraceptives.

Phytoestrogens

Phytoestrogens are naturally occurring plant substances with a chemical structure similar to 17-beta estradiol. They consist mainly of isofl avones found in high con-centrations in soy beans and other legumes and lignans found in a variety of fruits and vegetables. It is impor-tant to understand that isofl avones are weak estrogens compared to estradiol. Even more confusing is the fact that breast cancer incidence is much lower in Asia where diets are very high in soy compared to the US. However, the data linking soy intake and breast cancer are incon-sistent, with no strong evidence to promote high soy diets with either increased or decreased risk of breast cancer for women in the US. We, therefore, support the belief that soy is probably safe for women to consume in amounts similar to Asian diets.

Caffeine

While caffeine has long been thought of as a risk for increased breast pain, there are no studies to show a link between caffeine intake and breast cancer.31

Smoking

It is diffi cult to asses the risk of smoking and breast can-cer. Much like socioeconomic status, risk is likely linked to a number of factors. Such factors include increased incidence of alcohol consumption and endogenous hor-monal level infl uencing increased breast cancer risk.32,33

Breast Density

Increased breast density is known to impact the ability of mammograms to detect the presence of breast cancers. Additionally increased breast density (defi ned as greater than 75% density) is also thought to be an independent risk factor for developing breast cancer. Independent epidemiologic studies have shown a four to fi ve times greater risk of developing breast cancer in women with mammographically dense breasts compared to women of similar age with less dense breasts.34,35

Exposure to Ionizing Radiation

Exposure to ionizing radiation of the chest at a young age (as in treatment of Hodgkin lymphoma, the aban-doned practice of thyroid irradiation or in survivors of atomic bomb or nuclear plant accidents) is associated with an increased risk of breast cancer.36,37,38 It appears that the most vulnerable exposure age is peripubertal, from 10 to 14. After age 45, there does not appear to be any increased risk.

(Refer to Table 3: Risk Factors for Breast Cancer)

Prevention

After a woman engages in any lifestyle changes she can to decrease her risk of breast cancer (i.e., limited alcohol consumption, healthy weight and diet, exercise, avoid exogenous hormones and radiation exposure, having fi rst child at a younger age, and breast feeding at least 6 months), there may be a role for chemo prevention in high risk women. The use of drugs such as tamoxifen or raloxifene for fi ve years can reduce the risk of develop-ing breast cancer by 50%.39

Early Detection

Early detection is probably the single most important aspect in the management of breast cancer that we can impact. Early detection results in discovering lower stage cancers which directly translates into higher survival rates. This is illustrated by a near 100% survival rate for stage 1 breast cancer quoted by the American Cancer Society as compared to 20% survival seen in the most advanced breast cancers. Survival is inversely proportional to stage, thus illustrating the importance of early detection by means of self exam, practitioner clinical exam and imaging. Physical breast exam is a critical part of breast evaluation, as 20% of breast cancers are not visible on mammogram.

Mammography

Screening programs and mammography have revolu-tionized the fi eld of breast cancer. Forty years ago few patients presented with tumors less than 2 cm while today most cancers are diagnosed at less than 2 cm.40

The goals of screening are to identify those women with breast cancer at as early a stage as possible (thus reduc-ing mortality), to be safe and affordable, relative easy and available, and highly sensitive with a low rate of false positives. Mammography has proven a reproduc-ibly useful tool in numerous studies looking at hundreds of thousands of women in case control, cohort and randomized trials over the past 40 years.41


The age at which to start screening mammograms is an old and ongoing debate. To address this issue the Can-cer Screening Evaluation Unit conducted the “Age Trial,” directed at women 39 to 41, comparing annual screen-ing mammograms to routine medical care. This trial did demonstrate “a reduction in breast cancer mortality in the intervention group, in relative and absolute terms”, but did not reach statistical signifi cance. However, it is important to note that this study looked at a very narrow range of young women and would likely be more sticking had it included women 40-45 or 40-50.

Even more dramatic is the data recently presented, 9/29/10, during a press briefi ng in advance of the annual breast cancer symposium sponsored by the American Society of Clinical Oncology. The SCRY cohort (mam-mography screening in young women) a study out of Umeå (Sweden) University by Håkan Jonsson, Ph.D, and collegues, reviewed data involving over 1 million women from 1986-2005. In 1986 Sweden adopted national breast cancer screening quidelines, under which screen-ing mammography was optional for women 40-49 and 70-74 years old.

They found screening mammography in women 40-49 years reduced the risk of breast cancer mortality by 26% compared with women in that age group not screened. When only those who actually participated in the screen-ing were included, women in the study group had a 29% lower risk of dying from breast cancer. It should be noted that the researchers found that 1,250 women would need to be screened in order to save one life.42

(Refer to Table 4: National Organizations’ Screening Guidelines for Mammography)

Whether a woman should have a mammogram before the age of 40 should be based on physical fi ndings (pal-pable mass), family history, if there are other abnormal studies (i.e. ultrasound with suspicious fi nding) and level of clinical concern.

The opposite side of the debate is at what age to stop mammography. According to the National Center for Health Statistics, life expectancy for women in the United States in know quoted at 80.7 hitting an all time high. If a woman lives to 75, her life expectancy is another 12 years or more. Some have suggested that the screening interval be expanded to every other year after age 75.

Table 3: Risk Factors for Breast Cancer and Approximate Strength of AssociationReference from: Disease of the Breast, Lippincolt, Williams and Wilkins. 2004

Reproductive Factors

Hormonal FactorsNutritional/Lifestyle

FactorsOther Factors

Age of fi rst period – OC use (current vs. none) + Obesity (>27 BMI vs. (>_15 vs. 11)

Premenopausal Postmenopausal

–+

Family history (mother and sister)a

+++

Age at fi rst birth (>_35 vs. _5 yr vs. none)

+ Height (>5 feet 7 inches) + Jewish heritage (yes vs. no)

+

Age at menopause (5-yr increment)

+ Estrogen plus progesterone replacement

(>_5 yr vs. none)

++ Physical activity (>3 hr/wk)

Ionizing radiation (yes vs. no)

+

Breast-feeding(>1 yr vs. none)

– High blood estrogens (postmenopause)High blood IGF-I(premenopausal)

High blood prolactin

+++

+++

++

Monounsaturated fate

Saturated fat

Benign breast diseased

(MD diagnosed)d

++

Note: BMI, body mass index: IGF-I insulin-like growth factor type I; OC, oral contraceptives; +, relative risk (RR) = 1.1–1.4; ++, RR = 1.5–2.9; +++, RR = 3.0–6.9; –, RR = 0.7–0.8.(a) two fi rst degree relatives who have a history of breast cancer before the age 65 years versus no relative.(b) fi rst-degree relative who has a history of breast cancer before age 65 ys versus no relative(e) upper quartile (top 25%) verus lower quartile (lowest 25%)(d) clinically recognized chronic cystic, fi brocystic, or other benign breast disease versus none.


This is based on data showing that elderly women are more likely to have favorable cancer (ER +, well differen-tiated, node negative) than their younger counterparts.43 There are no set criteria on an absolute age at which mammograms should be stopped. We therefore feel this is a clinical judgment that should be decided by a woman’s primary care doctor on an individual case basis.

Breast Imaging

Breast imaging is critical in the detection, diagnosis and treatment of breast cancer. Mammography forms the foundation of breast imaging and has been used as both a screening and diagnostic tool for decades. Although patient history and physical exam are important, mam-mography usually detects breast cancer before it is clinically evident. Once an abnormality is detected with the mammogram, breast ultrasound is performed to further characterize the fi nding. Recently, breast MRI has emerged as a powerful tool for both the detection and staging of breast cancer. Other new breast imaging techniques, such as breast specifi c gamma imaging and positron emission mammography also fi ll a role similar to breast MRI.

Screening mammography has been proven to reduce breast cancer mortality in multiple studies.44 Mammogra-phy can detect breast masses and microcalcifi cations and is useful in characterization of both. Initially mammog-raphy was performed using fi lm-screen technique, but more recently digital mammography has replaced this technique at most facilities. Digital mammography uti-lizes x-rays and a digital detector to generate an image of the breast. Compared to other images generated with

x-rays, digital mammography is optimized for the breast, while minimizing radiation dose. Digital technique has been shown to improve detection of breast cancer in younger women and those with dense breasts.45 Digital images of the breast are also used during stereotactic biopsies to guide the needle in the area of the abnor-mality, usually microcalcifi cations or lesions occult by ultrasound.

Ultrasound utilizes high frequency sound waves to generate an image of breast tissue. Breast ultrasound has not been shown to be as benefi cial as a screening exam,46,47 and is used in the diagnostic setting only. This modality is employed after an abnormality is detected with mammography and for palpable abnormalities dis-covered by the patient or her clinician. Breast ultrasound can differentiate between solid and cystic masses with a high degree of accuracy and is helpful in characterizing lesions so the radiologist can determine if biopsy is nec-essary. Once a suspicious lesion is detected with ultra-sound, a core biopsy can be performed with ultrasound guidance. This procedure has a relatively high degree of comfort for the patient, and the radiologist can perform the biopsy with direct ultrasound visualization.

Breast MRI is a relatively new imaging modality that has positively impacted the diagnosis and treatment of breast cancer. This technique generates images by utilizing radiofrequency pulses in conjunction with a strong magnetic fi eld. The MRI signal refl ects density of water protons in tissue and their magnetic interactions with adjacent molecules. MRI depicts breast anatomy in remarkable detail. IV contrast is a necessary component of the exam because cancers tend to take up IV contrast

Table 4: National Organizations’ Screening Guidelines for Mammography Screening plays a major role in early detection, leading to greater chances for survival.

American Cancer Society (ACS)For women for normal risk, yearly mammograms are recommended starting at age 40. CBE suggested about every three years for women in their 30’s and every year for women age 40 and above. BSE is suggested for women starting in their 20s.

National Comprehensive Cancer Network (NCCN)Women at normal risk are recommended to have CBE every 1–3 years; periodic SBE is encouraged. Beginning at age 40, annual CBE and mammograms are recommended, and periodic SBE is encouraged.

National Cancer Institute (NCI)Women who are age 40 and above should be screened with mammograms every 1–2 years.

BSE, breast self-examination; CBE, clinical breast examination; SBE, self breast examination


early compared to normal breast tissue, and therefore can be detected by the radiologist. Breast MRI is usu-ally performed with patients that have a new diagnosis of breast cancer. It is also useful in patients with strong family history of breast cancer, dense breasts and problem solving after inconclusive mammography. This modality allows for detection of possible cancers in the opposite breast and often yields a more accurate dimen-sion of the known cancer.48 The detection and evalu-ation of invasive lobular cancer is another benefi t of breast MRI. This cancer can mimic normal breast tissue on mammography and ultrasound, but is demonstrated much more accurately with breast MRI.49

Other new modalities for breast imaging have recently become available. Two of these new modalities are breast specifi c gamma imaging (BSGI) and positron emission mammography (PEM). They both involve the IV injection of radioisotope with subsequent imaging.50 BSGI uses a radioisotope that collects in the mitochon-dria of cells. Since many breast cancers contain a higher density of mitochondria, the isotope will show increased uptake in the area of the cancer. BSGI can be used for many of the same indications as breast MRI. PEM re-quires a glucose analog that accumulates in glucose avid cells. Breast cancer cells usually have a higher metabolic rate than normal cells, and therefore the isotope will collect in these cells. Some breast centers are using PEM for preoperative evaluation of patients with known breast cancer, in a similar manner as breast MRI.

All of the above modalities have certain strengths and weakness. However, when utilized together in the appropri-ate patient population, they can signifi cantly improve breast cancer detection and care of patients with breast cancer.

Pathology

The pathologist is sometimes described as the “invis-ible” member of the multidisciplinary team that pro-vides care for patients with breast cancer. Nonetheless, pathology plays a critical role in virtually all aspects of breast cancer care, including initial diagnosis, tumor staging, treatment decisions, monitoring treatment ef-fectiveness, and prognostication.

The initial diagnosis of breast cancer is usually estab-lished via core needle biopsy. By examining a small core of breast tissue under the microscope, the pathologist can provide a wealth of information about the nature of a clinically or radiographically worrisome lesion.51 Is the lesion caused by a neoplastic process? If so, is the

neoplasm intraepithelial (so-called carcinoma in situ) or an invasive malignancy? What is the histologic type, sub-type, and grade of the tumor? Ductal type neoplasms may be managed signifi cantly differently from lobular types.52 Certain histologic subtypes of breast carcinoma – for example tubular and mucinous carcinomas – have a typically better prognosis,53 while other subtypes – such as micropapillary carcinoma – are more likely to be asso-ciated with lymph node metastases.54 Histologic grade also correlates with behavior, with higher-grade tumors usually behaving more aggressively.55

After the initial diagnosis of breast cancer is established, surgical removal and staging of the tumor is often the next step. Tumor size measurements and adequacy of surgical margins are important determinants of subse-quent treatment,56 which can be assessed by gross exami-nation in the pathology laboratory and most accurately documented by histopathologic examination under the microscope.57 Also, in patients who have received lo-coregional radiation and/or systemic hormone therapy or chemotherapy, microscopic examination can document whether the tumor has responded to treatment.58

The presence or absence of regional lymph node metastases is another critical factor that determines optimal treatment for each patient.59 Sentinel lymph node biopsy is a rapid method whereby a radioactive tracer or dye is injected in the vicinity of the tumor and drained by the lymphatic system.60 The fi rst node to show radioactivity or discoloration is a “sentinel” lymph node, i.e. a lymph node that will presumably be the fi rst to capture any tumor cells that may have invaded the lymphovascular space. During surgery, the patholo-gist performs a frozen section to immediately examine the sentinel lymph node under the microscope.61 If no histopathologic evidence of metastatic carcinoma is found, then the patient is unlikely to have metastases in other regional lymph nodes, and she can be spared a complication-prone axillary lymph node dissection. If, on the other hand, metastatic carcinoma is found in the sentinel node, then the surgeon will often proceed to perform a full axillary dissection to lessen the potential tumor burden. Although some very small metastases or isolated tumor cells may only be detected by subse-quent immunohistochemical or molecular methods,62 the elegance of sentinel lymph node biopsy is that in the vast majority of cases the pathologist can provide the surgeon with an accurate frozen section diagnosis to determine the course of surgery while the patient is still on the operating table.


Table 5: American Joint Committee on Cancer Staging System for Breast Cancer, 2007

Primary Tumor (T)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

Tis (DCIS) Ductal carcinoma in situ

Tis (LCIS) Lobular carcinoma in situ

Tis (Paget’s)

Paget’s disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) in the un-derlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget’s disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget’s disease should still be noted

T1 Tumor ≤ 20 mm in greatest dimension

T1mi Tumor ≤ 1 mm in greatest dimension

T1a Tumor >1 mm but ≤ 5 mm in greatest dimension

T1b Tumor >5 mm but ≤ 10 mm in greatest dimension

T1c Tumor >10 mm but ≤ 20 mm in greatest dimension

T2 Tumor >20 mm but ≤ 50 mm in greatest dimension

T3 Tumor >50 mm in greatest dimension

T4 Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules). Note: Invasion of the dermis alone does not qualify as T4

T4a Extension to the chest wall, not including only pectoralis muscle adherence/invasion

T4b Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d’orange) of the skin, which do not meet the criteria for infl ammatory carcinoma

T4c Both T4a and T4b

T4d Infl ammatory carcinoma (see “Rules for Classifi cation”)

Regional Lymph Nodes (N)

Clinical

NX Regional lymph nodes cannot be assessed (e.g., previously removed)

N0 No regional lymph node metastases

N1 Metastases to movable ipsilateral level I, II axillary lymph node(s)

N2 Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fi xed or matted; or in clinically detected * ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases

N2a Metastases in ipsilateral level I, II axillary lymph nodes fi xed to one another (matted) or to other structures

N2b Metastases only in clinically detected * ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastases

N3 Metastases in ipsilateral infraclavicular (level III axillary) lymph node(s) with or without level I, II axillary lymph node involvement; or in clinically detected * ipsilateral internal mammary lymph node(s) with clinically evident level I, II axillary lymph node meta stases; or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement

N3a Metastases in ipsilateral infraclavicular lymph node(s)

N3b Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s)

N3c Metastases in ipsilateral supraclavicular lymph node(s)

Distant Metastases (M)

M0 No clinical or radiographic evidence of distant metastases

cM0(i+) No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases

M1 Distant detectable metastases as determined by classic clinical and radiographic means and/or histologically proven larger than 0.2 mm


Table 6: American Joint Committee on Cancer Stage Grouping

STAGE TNM5-YEAR RELATIVE

SURVIVAL RATE (%)[*]

0 Tis, N0, M0 100

I T1, N0, M0 100

IIA

T0, N1, M0

92T1, N1, M0

T2, N0, M0

IIBT2, N1, M0

81T3, N0, M0

IIIA

T0, N2, M0

67

T1, N2, M0

T2, N2, M0

T3, N1, M0

T3, N2, M0

IIIB

T4, N0, M0

54T4, N1, M0

T4, N2, M0

IIIC Any T, N3, M0 [†]

IV Any T, any N, M1 20

* Breast Cancer Survival by Stage: American College of Surgeons National Cancer Data Base.

† These numbers are based on patients in whom cancer was diagnosed from 1995 to 1998. Five-year survival rates are not yet available for stage IIIC breast cancer because this stage was defi ned only recently.

In addition to the histologic features, there are a variety of other biological markers that indicate tumor behavior and the optimal treatment regimen. Tumors that retain receptors for estrogen and progesterone are more likely to respond to hormone therapy. The presence of estro-gen receptor (ER) or progesterone receptor (PgR) in the nuclei of tumor cells may be demonstrated by immuno-histochemistry, whereby a monoclonal antibody to the particular receptor initiates a chromogenic response which can be microscopically quantifi ed; appropriate tissue handling is essential to ensure these test results are accurate.63 Also, carcinomas that show amplifi ca-tion of the HER2/neu gene or over-express its protein product are eligible for treatment with Herceptin. HER2/neu protein over-expression is quantifi ed using immu-nohistochemistry, while gene amplifi cation is measured by fl uorescent in situ hybridization (FISH), a process in

which DNA probes labeled with fl uorescent dye attach (or “hybridize”) to the specifi c HER2/neu gene sequence in cells.64 Finally, immunohistochemistry for Ki-67 (also known as MIB-1) demonstrates the degree of proliferative activity in each case of breast cancer, which is another indication of tumor aggressiveness, since carcinomas showing higher proliferative activity usually behave more aggressively.65 All of these tumor markers and more can also be tested using sophisticated “gene chips” which measure the expression of several genes relevant to the development and progres-sion of breast cancer simultaneously.66

Pathologists at Southwest Washington Medical Center draw from a wide variety of techniques including gross anatomy, histopathology, immunohistochemistry and molecular diagnostics, to provide the breast cancer care multidisciplinary team with accurate information about the likely behavior of each individual tumor and its poten-tial responsiveness to therapy. In this manner, pathology helps the entire team strive for the promise of “personal-ized medicine”: that each individual patient receives the most effective treatment that is tailored to her individual situation, while minimizing its undesirable side effects.

Invasive Breast Cancer

Breast cancer is thought to be a process that develops from a preinvasive or in situ phase to invasive disease. During the initial phase normal cells continue to undergo enough genetic alterations to develop in situ disease and then onto malignant transformation.

Most infi ltrating breast cancers are adenocarcinomas arising in the terminal ducts. Invasive ductal carcinoma accounts for 85% of breast cancer and is often associated with DCIS. Invasive lobular is much less common account-ing for 5-15% of breast cancer. Lobular carcinomas tend to grow around the ducts and lobules and have similar prognosis, stage for stage, as Invasive Ductal carcinoma. There are several subtypes of invasive breast cancer, such as mucinous, papillary, tubular and adenoid which carry a better prognosis overall.

Advancements in understanding the biology of breast cancer have changed our approach from formula treat-ment to individualized treatment plans based on tumor biology and characteristic. Breast cancer treatment depended on a number of factors-initial stage of the cancer, cosmetic factors(size and location of the mass and breast size), other risk factors, history of breast cancer in the same breast, gene status, a history of previous breast surgeries and patient preference.


Treatment determination requires fi rst staging the breast cancer. This is primarily based on size of the mass, nodal involvement and metastatic or distant disease. However, tumor hormone receptor and the presence of the human epidermal growth factor receptor or HER 2, gene assays such as Oncotype (21 gene assays designed to assess recurrence risk), as well as the woman’s age and meno-pausal status are also important factors in determining individual treatment plans.

(Refer to Table 5: American Joint Committee on Cancer Staging System for Breast Cancer, 2002; Table 6: Ameri-can Joint Committee on Cancer Stage Grouping) (See Figure 5: Five-year Observed Survival – National; Figure 6: Five-year Observed Survival - Southwest)

Estrogen and progesterone play key roles in the devel-opment of both normal breast tissue and breast cancers. Estrogen expression (ER+) is found in approximately 70% of breast cancers and ER+ breast cancers are known to grow more slowly. The relationship between

Figure 5: Five-year Observed Survival – National National survival rates for breast cancer decline steadily according to stage.

Figure 6: Five-year Observed Survival – SouthwestSurvival rates for Southwest’s breast cancer patients closely follow national trends, with slightly better than national rates for those with Stage 2B and 3B.

0

2Years from diagnosis

3 4 5

10

20

30

40

50

60

70

80

90

100

Stage 0

Stage I

Stage IIA

Stage IIB

Stage IIIA

Stage IIIB

Stage IIIC

Stage IV

0

2Years from diagnosis

3 4 5

10

20

30

40

50

60

70

80

90

100

Stage 0

Stage I

Stage IIA

Stage IIB

Stage IIIA

Stage IIIB

Stage IIIC

Stage IV


estrogen expression and cancer initiation is unclear because ER+ cells are nonproliferative. Further, breast cancers have only a small percentage which actually expresses the receptor, and breast cancer stem cells do not express estrogen. Therefore, estrogen is thought to have an affect on neighboring proliferating cells. Most importantly antiestrogen treatment is effective in both preventing breast cancer recurrence and in slowing pro-gression in metastatic disease.

HER 2 protein overexpression, which is seen in approxi-mately 20% of breast cancers, is associated with a more aggressive clinical course and decreases survival com-pared to HER 2, not overexpressed cancers. The mecha-nism by which it functions is thought to be as a proto-oncogene, turning on other genes with subsequent down stream signal upregulation. This understanding has lead to the development of therapies directed against it such as trastuzumab, human monoclonal anti-body that binds HER 2, and in combination with chemo-therapy has been shown to prolong survival and de-crease recurrence rates by 50% in HER 2 + women.67,68

Lymph node status remains the single most predic-tive factor for breast cancer. Node positive disease is a strong indicator of recurrence risk. Sentinel lymph node dissection is the standard of care now with most experts recommending a 2-3 node harvest.

(Refer to Table 7: Axillary Node Status and Outcome in Operable Breast Cancer)

Management of Noninvasive Breast Cancer

Noninvasive ductal carcinoma or ductal carcinoma in situ (DCIS) is defi ned as proliferation of malignant cells con-fi ned within the basement membrane of the duct of the breast. Most DCIS are diagnosed by mammograms and are seen as a cluster of microcalcifi cations approximately 72% of the time, as calcifi cations and a soft tissue ab-normality 12% and only 10% of the time as a soft tissue abnormality alone. Generally speaking, DCIS is treated with local excision and radiation. This is widely accepted as the standard of care although several groups, such as Silverstein’s series from Van Nuys, have reported excel-lent local control rates with wide excision only.69,70

Sentinel Lymph Node Biopsy and DCIS

As DCIS is contained to the basement membrane of the duct cell there should be no potential for spread to the lymph nodes and therefore no need to perform SLN biopsy. However, several studies have documented a higher incidence of micrometastasis found on SLN bi-opsy for high risk DCIS (very large DCIS, DCIS associat-ed with a mass, high grade DCIS with comedonecrosis). This is likely a refl ection of small foci of invasive disease that was not found on pathology.71

Management of Invasive Breast Cancer

The management of breast cancer is multidisciplinary involving specialists in surgical oncology, breast imaging, medical and radiation oncology, reconstructive surgery and an ancillary team of nurse navigators, physical thera-pists, research staff and others. In the United States, thanks in large part to breast cancer awareness and

Table 7: Axillary Node Status and Outcome in Operable Breast Cancer

SURVIVAL (%) RELATED TO NODES

NEGATIVE NODES 1–3 POSITIVE NODES 4 POSITIVE NODES

Authors 5 Yr 10 Yr 5 Yr 10 Yr 5 Yr 10 Yr

Milan 89 [91] — 68 [53] — 48 [31] —

Royal Marsden 66 [69] — 70 [51] — 42 [32] —

M.D. Anderson — — 91 [69] — 53 [43] —

Carter et al. 92 — 81 — 57 —

Valagussa et al. 88 [79] 83 [74] 69 [46] 54 [33] 42 [26] 26 [15]

Ariel 81 63 66 53 48 23

Fisher et al. 78 65 62 38 32 13

Adapted from Yeh I, Fowble B, Viglione MJ, et al: Pathologic assessment and pathologic prognostic factors in operable breast cancer. In Fowble B, Goodman RI, Glick JH, Rosato EF (eds): Breast Cancer Treatment: A Comprehensive Guide to Treatment. St. Louis, Mosby-Year Book, 1991, p 171.


screening mammography, women are often diagnosed with small cancers less than 2 cm and are excellent can-didates for breast conservation therapy (BCT).

Early Breast Cancer, Breast Conservation and Radiation

BCT, surgically removing the cancer and preserving the breast, is a safe and viable option with recurrence risk near that of mastectomy when combined with radia-tion.72 This issue has been well studied including the hallmark NSABP B-06 trial that randomized women into three treatment arms; mastectomy, breast conservation with radiation, and breast conservation without radia-tion. They found that the “in breast failure rate” without radiation approached 40% and that when radiation was added recurrence risk fell to near mastectomy. This study was so convincing that it lead to the 1990 National Can-cer Institute consensus development conference on the treatment of early breast cancer, declaring BCT as pref-erable to mastectomy because it preserved the breast with all the attendant psychological and body imaging advantages associated with breast preservation.73

Contraindications to BCT

The primary obstacles to breast conservation are breast esthetics, risk of local recurrence (LR) or in breast recur-rence and patient preference. If the risk of in breast recurrence is greater than 15-20%, mastectomy is gener-ally recommended. Absolute indications for mastectomy would include failure to obtain clear margins, multi-centric disease, recurrent breast cancer or a history of previous radiation treatment to the breast, and preg-nancy (possible exception is third trimester with delayed radiation). Relative contraindications include breast size, centrally located tumor and breast esthetics post tumor excision, presence of BRCA 1&2 gene, and connective tissue diseases (scleroderma, lupus etc.).

(See Figure 7: Mastectomy vs. Conservation – Southwest)

Tumor Identifi cation and Excision

Lumpectomy or surgical removal of the tumor may be guided by palpation for larger masses which can be identifi ed on physical exam. Wire localization, where a wire is placed under image guidance (mammogram, US or MRI) by a radiologist prior to the procedure, helps identify the tissue to be excised for nonpalpable masses.

Axillary Staging

An integral part of cancer staging is assessment of dis-ease spread to the axilla with lymph node biopsy. Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the standard of care for clinically node negative breast cancers.74,75 SLN biopsy generally involves the use of blue dye (isosulfane blue) injected into the intradermal and subdermal tissue of the areola on the affected breast and radioisotope that is injected intradermally at the tumor site. The surgeon is then able to perform limited dissection on the ipsilateral axilla us-ing the blue dye and radioactivity to guide identifi cation of the sentinel nodes. The premise of the sentinel lymph nodes is to identify the fi rst draining nodes of the breast as they are most likely to contain cancer, if these nodes are negative there is very little chance of other nodes in the axilla containing cancer. By the use of SLN biopsy we are able to signifi cantly decrease the risks of axillary surgery; lymphedema (arm swelling), nerve injury (long thoracic and winged scapula, thoracodorsal nerve and branches of the costobrachial sensory nerve) and pain. Lymph node map-ping was originally described in 1977 and was extensively developed in the 1990s for the staging of melanoma.

The key question in the acceptance of SLN biopsy over complete axillary lymph node dissection for assessment of the axilla was the fear that false negative would result in increased risk of developing axillary local recurrence (LR). However, several observational studies76-80 and one randomized trial81 have demonstrated that LR following a negative SLN biopsy is rare, occurring in 0.2% of cases which is comparable to LR rate seen with ALND.

Figure 7: Mastectomy vs. Conservation – Southwest In 2009, 97% of breast cancer patients at Southwest were treated with surgery, and more than half of those patients were treated with conservation.

• Southwest breast cancer patients treated with conservation – 175 of 322 total cases = 54%• Southwest breast cancer patients treated with mastectomy – 137 of 322 total cases = 43%• Patients with no surgery – 9 of 322 = 3%Note: This includes Kaiser patients receiving surgery at SWMC by Kaiser surgeons.


Breast Radiation

Radiation therapy plays a common and important role in the management of breast cancer, either as a compo-nent of multidisciplinary care involved in curing breast cancer, or for palliation in the setting of advanced disease. The most common form of radiation therapy is external beam, in which a linear accelerator generates a beam, directed by clinicians to treat a tumor or region. The x-rays selectively kill cancer cells by damaging DNA, while normal tissue is spared signifi cant harm. Another common form of radiation called brachytherapy, relies on the insertion of a device or radioactive source directly into tissue; the beam generated by this radioactive source destroys nearby cancer cells. The limited range of this internal beam tends to minimize exposed normal tissue, resulting in fewer side effects.

Indications for radiation therapy to treat breast cancer include:

• After lumpectomy or mastectomy, either alone or in combination with chemotherapy and/or hormone therapy, to reduce the risk of cancer recurrence in the breast.

• As the main treatment for breast cancer if the tumor cannot be safely removed, if a woman’s health does not allow surgery, or if the woman chooses not to have surgery.

• To treat cancer that has spread into the bones or the brain.

• To relieve pain or other problems after a recurrence of the disease.

External beam radiation therapy is a painless treatment, often delivered in a series of sessions Monday through Friday, for three to eight weeks. Each treatment lasts less than 30 minutes, but varies depending on the type of treatment. Planning an individualized treatment re-quires procedure called “simulation” to create a proper patient setup, perform a CT scan, and temporarily mark the skin so each day the position can be recreated ac-curately. For most early stage breast cancers, the beam is directed only at the affected breast after surgery. For more locally advanced stages, nearby axillary and supra-clavicular lymph node areas are also treated.

Side effects of breast radiation therapy are usually temporary. Fatigue is common. Variable degrees of skin infl ammation are also seen, ranging from faint redness to signifi cant peeling and pain resembling a sunburn. There are late effects of radiation as well, including minor damage to a portion of one lung, hair loss in the axilla,

and brittle ribs that may be more prone to fracture. For left sided breast cancer there are concerns about risk of coronary artery disease long after treatment. Rarely a cancer may develop as a direct result of radiation treat-ment, years after the exposure and often near or within the treated area.

In the past 10 years, brachytherapy has played an in-creasingly active role in the management of early stage breast cancer. Breast brachytherapy involves placement of a single or series of catheter devices in the breast around a site from which a breast cancer was recently re-moved. Treatment is confi ned to this region with minimal exposure to other organs. As a result, fewer effects on organs close to the breasts, including the lungs, heart, ribs, muscles and skin, can be seen with proper patient selection. Furthermore, this breast cancer treatment can be given in a more condensed schedule than external beam. This short treatment course, often called accel-erated partial breast irradiation (APBI), allows breast cancer to be treated with radiation therapy in fi ve days instead of six to seven weeks of external beam. Side effects tend to be minimal but include fatigue, dermati-tis, infection, and long-term scarring or fl uid around the tumor cavity.

Typical indications include:

• Age of patient greater than 45-50• Small tumor• Clear surgical margins after a lumpectomy• Few or no lymph nodes involved

The long-term results of APBI techniques are still under study, but early results have been promising. In Fall 2010 Southwest’s radiation therapy unit will make APBI avail-able to appropriate patients.

Mastectomy and Breast Reconstruction

Mastectomy or complete removal of the breast gland has changed dramatically from the Halsted radical mas-tectomy with en bloc removal of the breast, skin, pecto-ralis major and minor muscles and axillary contents. The modern modifi ed radical mastectomy which includes removal of the breast gland and axillary contents and mastectomy with SLN biopsy (removal of the breast gland and lymph node sampling) are dramatically less invasive with equally dramatic improvement in the mor-bidity associated with more radical approaches. The key point in making the movement to less deforming and morbid procedures is the fact that the survival benefi t is equal.82-85


Reconstruction of the breast can often be started at the time of the mastectomy and advances in preservation of the breast envelope have developed dramatically since the 1980s with nipple sparing mastectomy (NSM) and skin sparing mastectomy (SPM) having been shown to be safe and viable options in carefully selected patient population by accomplished surgeons.86-88 NSM is a surgical technique that combines complete removal of the entire breast gland and coalescence of ducts imme-diately beneath the nipple to within 2-3 mm of the skin, with preservation of the breast envelope (dermis and epidermis). Most surgeons also perform an additional “coring out” of the posterior nipple tissue which is sent for frozen section during the procedure to confi rm no involvement of the NAC.

Selection criteria for NSM will continue to evolve as more long- and short-term data accrue. Keeping in mind that the indications for this procedure require a balance between clinical stage and tumor biology, inclusion should be considered in those breast cancer patients meeting the following criteria:89 (a) no clinical involve-ment of the NAC (including nipple discharge); (b) tumor size up to 3cm (pending nodal status); (c) tumor to nipple distance ≥2cm.

Multifocal tumors that meet these criteria can also be considered; however, those patients with multicentric disease are not candidates for NSM and should be considered for SSM. Although positive axillary status has not been consistently correlated with risk of nipple involvement, this procedure should be discouraged in patients with extensive axillary node metastasis. In addi-tion, most candidates for breast-conserving surgery who prefer to undergo mastectomy could be evaluated for NSM.

Chemotherapy

Chemotherapy treatment of breast cancer is now well established often helping cure patients with locally ad-vance breast cancer.. In the case of metastatic disease, a signifi cant improvement in quality of life and the pos-sibility of living for many years have also been observed with various treatment regimens.

(Refer to Table 8: Breast Cancer First Course Treatment by Stage – Southwest)

Chemotherapy drugs can be used in various combina-tions or treatment regimens. Commonly used drugs include anthracyclines such as Adriamycin, alkylating agents such as cyclophosphamide and taxanes such

Stage 0 Stage I Stage II Stage III Other Total

D,S 18 23 10 1 0 52

D,S,C 0 5 25 4 2 36

D,S,H 0 17 5 1 2 25

D,S,R 10 15 3 1 0 29

D,S,R,C 0 7 4 5 1 17

D,S,R,C,H 0 4 20 5 1 30

D,S,R,H 7 44 8 1 1 61

S 16 6 3 1 2 28

Other 7 17 14 2 4 44

Total 58 138 92 21 13 322

D = Diagnostic procedure

DS = Diagnostic procedure, surgery

D,S,C = Diagnostic procedure, surgery, chemotherapy

D,S,H = Diagnostic procedure, surgery, hormones

D,S,R = Diagnostic procedure, surgery, radiation

D,S,R,C = Diagnostic procedure, surgery, radiation and chemotherapy

D,S,R,C,H = Diagnostic procedure, surgery, radiation, chemotherapy and hormones

D,S,R,H = Diagnostic procedure, surgery, radiation and hormones

S = Surgery alone

Table 8: Breast Cancer First Course Treatment by Stage – SouthwestStage 1 cancers were most commonly treated with a combination of diagnostics, surgery, radiation and hormones.


as Taxol or Taxotere. Treatment may be administered before defi nitive surgery in what is called a neoadjuvant regimen to try to shrink down the tumor before oper-ating and also fi nd out more about the biology of the tumor. In very advanced, so called infl ammatory breast cancer, neoadjuvant chemotherapy can help make the tumor amenable to surgery and improve the chance of long-term survival. In the adjuvant setting, chemothera-py can be given safely and effectively over the course of approximately 4 months of treatment. A typical regime is dose-dense AC Taxol with treatments every 2 weeks for a total of 8 cycles. This has become one of the most widely used and well-established methods of treating breast cancer.

New drugs being developed for metastatic disease now include Abraxane and Ixempra. Chemotherapy drugs with signifi cant activity in breast cancer include gem-citabine, capecitabine, Navelbine, xeloda and 5-fl uo-rouracil, with many new drugs in the “pipeline” which should be available in the near future. Hormonal therapy is well established in the treatment of hormone positive i.e., estrogen receptor positive and/or progesterone receptor positive tumors. Aromatase inhibitors, such as Arimidex and Femara, have become standard therapy in treating postmenopausal women with breast cancer. They are generally well tolerated drugs and have had an important role in controlling and possibly curing this disease in conjunction with other methods of treatment. Tamoxifen is also effective in treating postmenopausal women. In premenopausal women with invasive disease it is considered standard therapy as is its use in women with noninvasive breast cancer or DCIS.

Biological therapy using monoclonal antibodies such as Herceptin for Her-2/neu overexpression in breast cancer tumors and Avastin which is somewhat controversial, have added greatly to our ability to treat disease, and Her-ceptin has a well-established role in Her-2/neu positive breast cancers. Other agents include Tykerb, which is a small molecular inhibitor which blocks specifi c receptors on certain breast cancers and can also help control ad-vanced or metastatic disease, with many other agents un-der development, which may have even greater benefi t.

We are still struggling to understand who needs to be treated and when and how aggressively. Tests that help us decide now include Oncotype testing which allows us to assess the relative benefi ts, if any, of chemotherapy in selected patients with ER and/or PR positive lymph node negative disease. Other measures of susceptibility

to various chemotherapy agents and such are also being developed and should be approved in the near future.

Finally, with regard to experimental therapies, there are investigators who still believe that the immune system needs to be properly stimulated using effective adju-vants and well-designed targets to create a greater degree of immunity in patients with breast cancer. We all hope that the future of breast cancer treatment will evolve to the point where the effective manipulation of the immune system will be one of the mainstays of therapy, but this treatment may be many decades away from effective implementation.

Cancer Research

Southwest has been promoting cancer research since 1986. The fi rst patient to be treated on a clinical trial at this institution was registered to a breast cancer study that same year. That was 24 years ago, and that same patient is still alive and doing well.

Over the years, Southwest has participated in hundreds of breast studies, becoming a leader in the advance-ment of new diagnosing techniques and treatments such as fi ne needle aspirations, core needle biopsies, modi-fi ed radical mastectomies, lumpectomies with radiation, and sentinel node biopsies vs. full axillary node dissec-tions, Tamoxifen for ER and/or PR positive tumors, the use of Adriamycin and Cytoxan, the addition of Taxol, the use of aromatase inhibitors for post-menopausal women, and recently, the use of Oncotype DX to deter-mine treatment, and the use of Herceptin for HER2-pos-itive tumors. We continue to champion new treatments and improvements to time-honored, research-proven therapies. Currently, we are participating in treatments that include surgical studies using neo-adjuvant treat-ment followed by sentinel node surgery, partial breast irradiation following lumpectomy, targeted therapies for metastatic breast cancer, and circulating tumor cells to indicate appropriate therapy (also for metastatic breast cancer). We also have several studies for high-risk tumors, as well as treatment studies for various stages of breast cancer. We are also looking at a study that will use new techniques for diagnosing breast cancer, hope-fully with as much as 100% accuracy.

Southwest remains on the cutting edge of breast cancer diagnosis, treatment, and follow-up care using research-proven therapies to benefi t our community. Our hats are off to the brave, selfl ess women who have advanced breast cancer care through research.


Figure 8: Ten-year Cancer Incidence – Southwest 2000-2009The number of breast cancer cases peaked in 2009.

1300

1250

1200

1150

1100

1050

1000

9502008

Year20092000 2001 2002 2003 2004 2005 2006 2007

1057

Num

ber

of

Cas

es 1183 1173

1265

1214 1214

12551232 1229

1191

Southwest WA State National

Site Number Percent Number Percent Number Percent

Breast 322 25 4,520 14 194,280 13

Lung & Bronchus

151 12 4,130 13 219,440 15

Colorectal 131 10 2,890 9 146,970 10

Prostate 81 6 4,680 15 192,280 13

Corpus/Uterus 70 6 960 3 42,160 3

Melanoma 63 5 1,970 6 68,720 5

Lymphoma 58 5 1,540 5 74,490 5

Brain/Other Nervous System

48 4 * * * *

Bladder 45 4 1,660 5 70,980 5

Thyroid 29 2 * * * *

Other 267 21 * * * *

Total 1,265 100 32,290 100 1,479,350 100

Washington State and National Data from ACS Cancer Facts and Figures 2009

*fi gures not available

Table 9: Comparative Cancer Incidence – 2009 In 2009, breast cancer was the number one cancer incidence site at Southwest, accounting for 25 percent of all incidences – exceeding both Washington state (14%) and national (13%) percentages.


Figure 9: Southwest Frequency of Cancer by Gender – 2009 Top Ten SitesThyroid cancer was more often sited in women (25) than men (4) at Southwest in 2009. The opposite was found with bladder cancer with more sited in men (34) than women (11).

140

120

100

80

60

40

20

0 0Breast Lung/

BronchusColorectal Prostate Uterus

Num

ber

of

Cas

es

Stage 0

Stage 1

Stage 2

Stage 3

Stage 4

Unknown0 2 1

58

138

92

21

112

434951

17 10

2733 33

21

9

54

18

60

50

723

8

160

Figure 10: Southwest Major Cancers – Stage at Diagnosis – 2009In 2009 at Southwest, more than half of the breast cancer cases (196 of 322) were diagnosed at Stage 0 or 1. When cancer is diagnosed and treated in its earliest stages, the chances for survival are greatest.

Thyroid

Bladder

Brain/Other Nervous System

Lymphoma

Melanoma

Uterus

Prostate

Colorectal

Lung/Bronchus

Breast

0

4318

6883

6764

81

7024

39

34242325

3411

425

50 100 150 200 250 300 350

Number of Cases

Site


Primary Site: Number of cases %Oral Cavity and Pharynx 15 1.2Tongue 6 0.5Floor of Mouth 2 0.2Gum & Other Mouth 1 0.1Tonsil 3 0.2Hypopharynx 2 0.2Other Oral Cavity & Pharynx 1 0.1Digestive System 206 16.3Esophagus 9 0.7Stomach 13 1.0Small Intestine 9 0.7Colon 100 7.9Rectum and Rectosigmoid 31 2.5Anus and Anal Canal 3 0.2Liver & Intrahepatic Bile Duct 9 0.7Gallbladder 2 0.2Other Biliary 5 0.4Pancreas 24 1.9Peritoneum, Omentum & Mesentery 1 0.1Respiratory System 153 12.1Larynx 2 0.2Bronchus and Lung 151 11.9Bones and Joints 2 0.2Soft Tissue (including Heart) 10 0.8Skin excluding Basal & Squamous 64 5.1Malignant Melanoma – Skin 63 5.0Other Non-epithelial Skin 1 0.1Breast 322 25.5Female Breast 318 25.2Male Breast 4 0.3Female Genital System 118 9.3Cervix 13 1.0Corpus Uteri 70 5.5Ovary 21 1.7Vagina 1 0.1Vulva 13 1.0Male Genital System 96 7.6Prostate 81 6.4Testis 15 1.2Urinary System 82 6.5Urinary Bladder 45 3.6Kidney & Renal Pelvis 35 2.8Ureter 2 0.2Brain & Other Nervous System 48 3.8Brain 18 1.4Other Nervous System 30 2.4Endocrine System 33 2.6Thyroid gland 29 2.3Other Endocrine (including Thymus) 4 0.3Lymphomas 58 4.6Hodgkin’s lymphoma (nodal) 6 0.5Non-Hodgkin’s lymphoma (Nodal=37, Extranodal=15) 52 4.1Myeloma 7 0.6Leukemia 19 1.5Lymphocytic Leukemia 6 0.5Myeloid & Monocytic Leukemia 10 0.8Other Leukemia 3 0.2Mesothelioma 3 0.2Kaposi Sarcoma 1 0.1Ill-Defi ned/Unspecifi ed 28 2.2

Table 10: Southwest Primary Site Table – 2009Breast and lung cancer were most frequently identifi ed as the primary cancer sites at Southwest in 2009.


Southwest Regional Cancer Center Registry Data Summary – 2009

Southwest Washington Medical Center’s Cancer Registry accessioned 1,265 new cases that were diagnosed in 2009 and provided follow-up data on more than 25,000 primaries gathered in our system. These data, including demographics, staging and treatment, are reported to the Washington State Cancer Registry and the National Cancer Database (NCDB) for use in monitoring cancer in-cidence and treatment trends in our state and the nation.

(Refer to Figure 8: Ten-year Cancer Incidence – Southwest 2000-2009; Table 9: Comparative Cancer Incidence – 2009) (See Figure 9: Southwest Frequency of Cancer by Gender – 2009; Figure 10: Southwest Major Cancers – Stage at Diagnosis – 2009) ( Refer to Table 10: Southwest Primary Site Table - 2009)

REFERENCES:1. Ries L, Young J, Keel G, et al: SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988–2001, Patient and Tumor Characteristics, Bethesda, MD, National Cancer Institute, SEER Program NIH Pub. No. 07–6215, 2007. (http://www.seer.cancer.gov/publications/survival/)/website/view?area=be&URL=http://www.seer.cancer.gov/publications/survival/

2. Jemal, A, Siegel, R, Ward, E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009; 59:225.

3. www.ancer.gov/cancertopics/factsheet/Detection/probability-brest –cancer.

4. Parkin, DM et. al Global cancer statistics 2002. CA Cancer J Clin 2005; 55:47.

5. The decrease in breast CA incidence in 2003 in the US. – Ravdin PM – N Engl J Med – 19-APR-2007; 356 (16): 1670-4.

6. Willett, WC et al, Non genetic factors in breast cancer In Harris JR ed Disease of the breast. 3rd ed. Philadelphia: Lippincott; 2004: 223-276.

7. American Cancer society breast cancer facts and fi gures.

8. Carey, LA, Perou, CM, Livasy, CA, et al. Race, breast cancer sub-types, and survival in the Carolina Breast Cancer Study. JAMA 2006; 295:2492.

9. Worsham, MJ et al. Multiplicity of benign breast lesions is a risk factor for progression to breast cancer. Clin Cancer Res 2007; 13: 5474.

10. Haagensen, CD, Bodian, C, Haagensen, DE. Lobular neoplasia (lobular carcinoma in situ) breast carcinoma: risk and detection. WB Saunders, Philadelphia 1981. p.238.

11. Chuba PJ, et al. Bilateral risk for subsequent breast cancer after lobular carcinoma-in-situ: analysis of the surveillance, epidemiology, and end results data. J Clin Oncolo. 2005 Aug 20; 23(24): 5534-41.

12. Fisher, B, Dignam, J, Wolmark, N, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 1999; 353:1993.

13. Sinletary et al. Alcohol and breast cancer: review of the epidemiol-ogy and experimental evidence and potential mechanism. JAMA 2001 Nov 7;286(17):2143-51.

14. Zhang SM et al. Plasma folate, vit B6, Vit B12, homocystine, and the risk of breast cancer. J Natl Cancer Inst 2003; 95:373-380.

15. Chen WT et al. Use of postmenopausal hormones, alcohol, and the risk for invasive breast caner. Ann Intern Med 2002 Nov 19; 137 (10):798-804.

16. Sinletary et al. Alcohol and breast cancer: review of the epidemiol-ogy and experimental evidence and potential mechanism. JAMA 2001 Nov 7;286(17):2143-51.

17. Smith-Warner SA, Spiegelman D, Adami HO, et al: Types of dietary fat and breast cancer: a pooled analysis of cohort studies. Int J Cancer 2001; 92:767-774.

18. Holmes MD, Colditz GA, Hunter DJ, et al: Meat, fi sh and egg intake and risk of breast cancer. Int J Cancer 2003; 104:221-227.

19. Reeves GK, Beral V, Green J, et al: Hormonal therapy for meno-pause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 2006; 7:910-918.

20. Morimoto, LM, White, E, Chen, Z, et al. Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Causes Control 2002; 13:741.

21. Feigelson, HS, Jonas, CR, Teras, LR, et al. Weight gain, body mass index, hormone replacement therapy, and postmenopausal breast cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev 2004; 13:220.

22. Ahn, J, Schatzkin, A, Lacey, JV Jr, et al. Adiposity, adult weight change, and postmenopausal breast cancer risk. Arch Intern Med 2007; 167:2091.

23. Hankinson, SE, Willett, WC, Manson, JE, et al. Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmeno-pausal women. J Natl Cancer Inst 1995; 87:1297.

24. Calle, EE, Rodriguez, C, Walker-Thurmond, K, Thun, MJ. Over-weight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348:1625.

25. Heck KE, et al, Explaining the relationship between education and postmenopausal breast cancer. Amer J Epidemiol 1997; 145:366-372. C:\online\content\abstract.do?topicKey=breastcn\9760&refNum=28

26. Berstein L, et al Endogenous hormones and breast cancer risk. Epidemiology Rev 1993; 15;48-62.

27. Russo, J, et al Differentiation of the mammary gland and suscepti-bility to carcinogenesis. Breast Cancer Res Treat 1982;2:5-73.

28. Collaborative Group of Hormonal factors in Breast Cancer. Lancete 2002;360:187-195.

29. Trichopoulos D et al, Menapause and Breast Cancer Risk. J Natl Cancer Inst 1972; 48:605-613.

30. Chen, WY et al Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast cancer. Cancer 2004; 101:1490.

31. Ganmaa, D, Willett, WC, Li, TY, et al. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer 2008; 122:2071.

32. Ishitani, K, Lin, J, Manson, JE, et al. Caffeine consumption and the risk of breast cancer in a large prospective cohort of women. Arch Intern Med 2008; 168:2022.


33. Band, P, Le, N, Fang, R, Deschamps, M. Carcinogenic and endo-crine disrupting effects of cigarette smoke and risk of breast cancer. Lancet 2002; 360:1044.

34. Boyd, NF, Guo, H, Martin, LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med 2007; 356:227.

35. McCormack, VA, dos Santos, Silva I. Breast density and parenchy-mal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2006; 15:1159.

36. Kenney, LB, Yasui, Y, Inskip, PD, et al. Breast cancer after child-hood cancer: a report from the Childhood Cancer Survivor Study. Ann Intern Med 2004; 141:590.

37. Guibout, C, Adjadj, E, Rubino, C, et al. Malignant breast tumors after radiotherapy for a fi rst cancer during childhood. J Clin Oncol 2005; 23:197.

38. Ostroumova, E, Preston, DL, Ron, E, et al. Breast cancer incidence following low-dose rate environmental exposure: Techa River Cohort, 1956-2004. Br J Cancer 2008; 99:1940.

39. . Fisher B, Costantino JP, Wickerham DL, et al: Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005; 97:1652-1662.

40. U Veronesi, et al, Conservative Treatment of Early Breast Cancer, long term results of 1232 Cases Treated with Quadrantectomy Axillary Dissection and Radiation. What’s new in General Surgery Vol 211. N0 2; 250-259.

41. Humphrey LL, Helfand M, Chan BK, et al: Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002; 137:347-360.

42. Swedish study: Håkan Jonsson, Ph.D. of the department of cancer epidemiology at Umeå (Sweden) Univerisity.

43. Tabar L, et al The Swedish Two-Country Trial twenty years years later. Updated mortality results and new insight from long term follow-up. Radiol Clin North Am 2000; 38:625-651.

44. Nystrim L, Rutquist LE, Wall S, et al. Breast cancer screening with mammography: overview of Swedish randomized trials. Lancet 1993;341:973-978.

45. Piasano ED, Gastsonis C, Hendrick E, et al. Diagnostic Perfor-mance of Diital versus Film Mammography for Breast Cancer Screen-ing. N England J Med 2005; 353:1773-1783.

46. Sickles EA, Filly RA, Callen PW. Breast cancer detection with sonography and mammography: comparison using state-of-the-art equipement. AJR Am J Roentgenol 1983; 140:843-845.

47. Kopans DB, Meyer JE, Lindfors KK. Whole-breast US imaging: four-year follow-up. Radiology 1985; 157:5050-507.

48. Hollingsworth AB, Stough RG, O’Dell CA, et al. Breast MRI for the preoperative locoregional staging. Am J Surg 2008; 196:389-396.

49. Weinstein SP, Orel SG, Heller R, et al. MR imaging of the breast in patients with invasive lobular carcinoma. AJR Am J Roentgenol 2001; 176:399-406.

50. Birdwell R, Mountford C, Iglehart JD, et al. Molecular imaging of the breast. AJR 2009; 193:367-376.

51. Bilous M. Breast core needle biopsy: issues and controversies. Mod Pathol. 2010 May;23 Suppl 2:S36-45.

52. Tavassoli FA. Lobular neoplasia: evolution of its signifi cance and morphologic spectrum. Int J Surg Pathol. 2010 Jun;18(3 Suppl):174S-177S.

53. Adeyinka A, Mertens F, Idvall I, Bondeson L, Ingvar C, Heim S, Mi-telman F, Pandis N. Cytogenetic fi ndings in invasive breast carcinomas with prognostically favourable histology: a less complex karyotypic pattern? Int J Cancer. 1998 Aug 21;79(4):361-4.

54. Ueng SH, Mezzetti T, Tavassoli FA. Papillary neoplasms of the breast: a review. Arch Pathol Lab Med. 2009 Jun;133(6):893-907.

55. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403-10.

56. Pleijhuis RG, Graafl and M, de Vries J, Bart J, de Jong JS, van Dam GM. Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions. Ann Surg Oncol. 2009 Oct;16(10):2717-30.

57. Dadmanesh F, Fan X, Dastane A, Amin MB, Bose S. Comparative analysis of size estimation by mapping and counting number of blocks with ductal carcinoma in situ in breast excision specimens. Arch Pathol Lab Med. 2009 Jan;133(1):26-30.

58. Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer bur-den to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22.

59. Danko ME, Bennett KM, Zhai J, Marks JR, Olson JA Jr. Improved staging in node-positive breast cancer patients using lymph node ra-tio: results in 1,788 patients with long-term follow-up. J Am Coll Surg. 2010 May;210(5):797-805.e1, 805-7.

60. Tafra L, Lannin DR, Swanson MS, Van Eyk JJ, Verbanac KM, Chua AN, Ng PC, Edwards MS, Halliday BE, Henry CA, Sommers LM, Car-man CM, Molin MR, Yurko JE, Perry RR, Williams R. Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye. Ann Surg. 2001 Jan;233(1):51-9.

61. Weaver DL. Pathology evaluation of sentinel lymph nodes in breast cancer: protocol recommendations and rationale. Mod Pathol. 2010 May;23 Suppl 2:S26-32.

62. de Boer M, van Dijck JA, Bult P, Borm GF, Tjan-Heijnen VC. Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases. J Natl Cancer Inst. 2010 Mar 17;102(6):410-25.

63. Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohis-tochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010 Jun 1;28(16):2784-95.


64. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF; American Society of Clinical Oncology/College of American Pa-thologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131(1):18-43.

65. Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010 Feb;11(2):174-83.

66. Ross JS. Multigene classifi ers, prognostic factors, and predictors of breast cancer clinical outcome. Adv Anat Pathol. 2009 Jul;16(4):204-15.

67. Smith I, Procter M, Gelber RD, et al: 2-year follow-up of trastu-zumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369:29-36.

68. Romond EH, Perez EA, Bryant J, et al: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353:1673-1684.

69. Silverstein MJ, Lagios MD, Groshen S, et al: The infl uence of mar-gin width on local control of ductal carcinoma in situ of the breast. N Engl J Med 1999; 340:1455-1461.

70. Silverstein MJ: The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg 2003; 186:337-343.

71. Cody 3rd HS: Sentinel lymph node biopsy for DCIS: are we ap-proaching consensus?. Ann Surg Oncol 2007; 14:2179-2181.

72. Fisher B, Anderson S, Bryant J, et al: Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast can-cer. N Engl J Med 2002; 347:1233-1241.

73. Kaufmann M, von Minckwitz G, Smith R, et al: International expert panel on the use of primary (preoperative) systemic treatment of oper-able breast cancer: review and recommendations. J Clin Oncol 2003; 21:2600-2608.

74. Veronesi U, Paganelli G, Viale G, et al: A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003; 349:546-553.

75. Clarke D, Khonji NI, Mansel RE: Sentinel node biopsy in breast cancer: ALMANAC trial. World J Surg 2001; 25:819-822.

76. Smidt ML, Janssen CM, Kuster DM, et al: Axillary recurrence after a negative sentinel node biopsy for breast cancer: incidence and clini-cal signifi cance. Ann Surg Oncol 2005; 12:29-33.

77. Jeruss JS, Winchester DJ, Sener SF, et al: Axillary recurrence after sentinel node biopsy. Ann Surg Oncol 2005; 12:34-40.

78. Blanchard DK, Donohue JH, Reynolds C, et al: Relapse and mor-bidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer. Arch Surg 2003; 138:482-487.

79. Chung MA, Steinhoff MM, Cady B: Clinical axillary recurrence in breast cancer patients after a negative sentinel node biopsy. Am J Surg 2002; 184:310-314.

80. Reitsamer R, Peintinger F, Prokop E, et al: Sentinel lymph node bi-opsy alone without axillary lymph node dissection–follow up of sentinel lymph node negative breast cancer patients. Eur J Surg Oncol 2003; 29:221-223.

81. U, Paganelli G, Viale G, et al: A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003; 349:546-553.

82. Turner L; Swindell R; Bell WG; Hartley RC; Tasker JH; Wilson WW; Alderson MR; Leck I.M. Radical versus modifi ed radical mastectomy for breast cancer. Ann R Coll Surg Engl 1981 Jul;63(4):239-43.

83. Maddox WA; Carpenter JT Jr; Laws HL; Soong SJ; Cloud G; Urist MM; Balch C.M. A randomized prospective trial of radical (Halsted) mastectomy versus modifi ed radical mastectomy in 311 breast cancer patients. Ann Surg 1983 Aug;198(2):207-12.

84. Fisher B; Redmond C; Fisher ER; Bauer M; Wolmark N; Wicker-ham DL; Deutsch M; Montague E; Margolese R; Foster R. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med 1985 Mar 14;312(11):674-81.

85. Fisher B; Jeong JH; Anderson S; Bryant J; Fisher ER; Wolmark N. Twenty-fi ve-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by ir-radiation. N Engl J Med 2002 Aug 22;347(8):567-75.

86. Sacchini V, Pinotti JA, Barros AC, et al: Nipple-sparing mastectomy for breast cancer and risk reduction: oncologic or technical problem?. J Am Coll Surg 2006; 203:704-714.

87. Gerber B, Krause A, Reimer T, et al: Skin-sparing mastectomy with conservation of the nipple-are

Documents

EMjournal Vol3N1 RS - PeaceHealth...Southwest Regional Cancer Center • 2010 Annual Report Incidence T he risk of a woman developing breast cancer, invasive and ductal carcinoma in