Treatmentofbreastcancer 110514142146 Phpapp01

8/12/2019 Treatmentofbreastcancer 110514142146 Phpapp01

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Treatment of breast

cancerDr.Syed Alam Zeb


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Classification

Carcinoma, NOS (not otherwisespecified).

Ductal. Intraductal (in situ). Invasive with predominant intraductal

component. Invasive, NOS. Comedo. Inflammatory. Medullary with lymphocytic infiltrate. Mucinous (colloid).

Papillary. Scirrhous. Tubular. Other.

Lobular. In situ. Invasive with predominant in situ

component. Invasive.

Nipple. Pagets disease, NOS. Pagets disease with intraductal

carcinoma. Pagets disease with invasive ductal

carcinoma.

Other. Undifferentiated carcinoma.


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Staging

TX: Primary tumor cannot be assessed

T0: No evidence of primary tumor

Tis: Intraductal carcinoma, lobular

carcinoma in situ, or Pagets disease ofthe nipple with no associated invasionof normal breast tissue

Tis (DCIS): Ductal carcinoma in situ Tis (LCIS): Lobular carcinoma in situ Tis (Paget's): Paget's disease of the

nipple with no tumor. [Note: Paget'sdisease associated with a tumor isclassified according to the size of thetumor.]

T1: Tumor 2.0 cm in greatestdimension

T1mic: Microinvasion 0.1 cm ingreatest dimension

T1a: Tumor >0.1 cm but 0.5 cm ingreatest dimension

T1b: Tumor >0.5 cm but 1.0 cm in

greatest dimension T1c: Tumor >1.0 cm but 2.0 cm in

greatest dimension

T2: Tumor >2.0 cm but 5.0 cm ingreatest dimension

T3: Tumor >5.0 cm in greatestdimension


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Staging (cont)

T4: Tumor of any size with direct extension to (a)chest wall or (b) skin, only as described below

T4a: Extension to chest wall, not includingpectoralis muscle

T4b: Edema (including peau dorange) or ulcerationof the skin of the breast, or satellite skin nodulesconfined to the same breast

T4c: Both T4a and T4b

T4d: Inflammatory carcinoma

Regional lymph nodes (N) NX: Regional lymph nodes cannot be assessed

(e.g., previously removed)

N0: No regional lymph node metastasis

N1: Metastasis to movable ipsilateral axillary lymph

node(s)

N2: Metastasis to ipsilateral axillary lymph node(s)fixed or matted, or in clinically apparent ipsilateralinternal mammary nodes in the absenceof clinicallyevident lymph node metastasis N2a: Metastasis in ipsilateral axillary lymph nodes fixed

to one another (matted) or to other structures

N2b: Metastasis only in clinically apparent* ipsilateralinternal mammary nodes and in the absence ofclinically evident axillary lymph node metastasis


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Staging (cont)

N3: Metastasis in ipsilateralinfraclavicular lymph node(s) withor without axillary lymph nodeinvolvement, or in clinicallyapparent* ipsilateral internalmammary lymph node(s) and inthe presenceof clinically evidentaxillary lymph node metastasis;or, metastasis in ipsilateralsupraclavicular lymph node(s)with or without axillary or internalmammary lymph nodeinvolvement

N3a: Metastasis in ipsilateralinfraclavicular lymph node(s)

N3b: Metastasis in ipsilateralinternal mammary lymph node(s)and axillary lymph node(s)

N3c: Metastasis in ipsilateralsupraclavicular lymph node(s)

Distant metastasis (M) MX: Presence of distant

metastasis cannot be assessed M0: No distant metastasis M1: Distant metastasis


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Staging (cont)

Stage 0

Tis, N0, M0

Stage I

T1*, N0, M0

Stage IIA

T0, N1, M0

T1, N1, M0

T2, N0, M0

Stage IIB

T2, N1, M0

T3, N0, M0

Stage IIIA T0, N2, M0 T1*, N2, M0 T2, N2, M0

T3, N1, M0 T3, N2, M0 Stage IIIB T4, N0, M0

T4, N1, M0 T4, N2, M0 Stage IIIC Any T, N3, M0 Stage IV Any T, Any N, M1


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Breast cancer is commonly treatedby various combinations of:

Surgery

radiation therapy

chemotherapy, and hormone therapy.


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Prognosis and selection of therapymay be influenced by:

the age and menopausal status

stage,

histologic and nuclear grade of theprimary tumor,

estrogen-receptor (ER) and progesterone-

receptor (PR) status, measures of proliferative capacity, and

HER2/neu gene amplification.


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menopausa s a us varywidely, some studies have

substituted age older than50 years as a surrogate for

the postmenopausal state.

f ll


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Patient management followinginitial suspicion of breast cancer

generally includes: Confirmation of the diagnosis, Evaluation of stage of disease,

Establishment of unilateral or bilateraldisease

Selection of therapy.

D l C i I Si


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Ductal Carcinoma In Situ

Ductal carcinoma in situ (DCIS) is a noninvasive,precancerous condition.

DCIS can progress to become invasive cancer,but estimates of the likelihood of this vary

widely. DCIS accounts for about 18% of all newly

diagnosed invasive plus noninvasive breasttumors in the United States.

Very few cases of DCIS present as a palpablemass; 80% are diagnosed by mammographyalone


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L b l C i I Sit


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Lobular Carcinoma In Situ

Strictly speaking, it is not known to be apremalignant lesion, but rather a marker thatidentifies women at an increased risk for

subsequent development of invasive breastcancer. This risk remains elevated even beyond2 decades, and most of the subsequent cancersare ductal rather than lobular.

LCIS is usually multicentric and is frequentlybilateral.


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Carcinoma In Situ

Most women with LCIS can be managed withoutadditional local therapy after biopsy.

No evidence is available that re-excision to obtain clearmargins is required.

Tamoxifen has decreased the risk of developing breastcancer in women with LCIS and should be considered inthe routine management of these women

Bilateral prophylactic mastectomy is sometimesconsidered an alternative approach for women at highrisk for breast cancer.

Axillary lymph node dissection is not necessary.


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Treatment options for patientswith LCIS

Observation after diagnostic biopsy.

Tamoxifen to decrease the incidence of

subsequent breast cancers.

Ongoing breast cancer prevention trials.

Bilateral prophylactic total mastectomy, withoutaxillary node dissection.

M t f St I II


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Management of Stage I, II,IIIA, and Operable IIIC Breast

Cancer Locoregional therapy Surgery

Radiation therapy

Adjuvant therapy

Hormonal therapy Chemotherapy


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Locoregional therapy

After the presence of a malignancy is confirmed andhistology is determined, treatment options should bediscussed with the patient before a therapeuticprocedure is selected.

The surgeon may proceed with a definitive procedure

Estrogen-receptor (ER) and progesterone-receptor (PR)status should be determined for the primarytumor.Additional pathologic characteristics, includinggrade, proliferative activity, and human epidermalgrowth factor receptor 2 (HER2/neu) status, may also beof value.


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Options for surgical managementof the primary tumor include:

breast-conserving surgery plus radiationtherapy,

mastectomy plus reconstruction, and

mastectomy alone.


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Selection of a local therapeuticapproach depends on:

the location of the lesion

size of the lesion

analysis of the mammogram breast size, and

the patients attitude toward preserving

the breast.


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relative contraindications to breast-conserving therapy

The presence of multifocal disease in the breast

history of collagen vascular disease.

A patients age should not be a determiningfactor in the selection of breast-conservingtreatment versus mastectomy

Whether young women with germ-line

mutations or strong family histories are goodcandidates for breast-conserving therapy is notcertain.


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surgical techniques used include:

Lumpectomy

Quadrantectomy

segmental mastectomy


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Which option?

Patients whose tumors have these characteristics

may benefit from a more generous initial excision

to avoid the need for a re-excision:

1. large tumors (T2 lesions),

2. positive axillary nodes,

3. extensive intraductal component,

4. palpable tumors, and

5. lobular histology


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Dealing with axillary lymph nodes

Axillary node dissection even in the presence ofclinically negative nodes is a necessary stagingprocedure.

Controversy exists as to the extent of the

procedure because of long-term morbidity

The standard evaluation usually involves only alevel I and II dissection, thereby removing a

satisfactory number of nodes for evaluation (i.e.,6-10 at a minimum), while reducing morbidityfrom the procedure.


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Sentinel lymph node biopsy

The SLN is defined as the first node in the lymphatic basin thatreceives primary lymphatic flow.

Studies have shown that the injection of technetium-labeled sulfurcolloid, vital blue dye, or both around the tumor or biopsy cavity, orin the subareolar area, and subsequent drainage of thesecompounds to the axilla results in the identification of the SLN in

92% to 98% of patients These reports demonstrate a 97.5% to 100% concordance between

SLN biopsy and complete axillary lymph node dissection The results of a randomized trial of 532 patients with T1 carcinomas

undergoing either SLN biopsy plus complete axillary dissection orSLN biopsy alone showed no axillary recurrences in either group and

no difference in the 3-year disease-free survival The reported false-negative rates (i.e., the number of patients with

negative SLN biopsy divided by the number of patients with positiveaxillary nodes at the time of axillary node dissection) of SLN biopsyrange from 0% to 10%.


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Radiation therapy

Following Breast conservation

Following mastectomy


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Radiation therapy following Breastconservation

Postoperative external-beam radiation therapy to theentire breast with doses of 45 Gy to 50 Gy, in 1.8 Gy to2.0 Gy daily fractions over a 5-week period.

Shorter hypofractionation schemes achieve comparableresults.

A further radiation boost is commonly given to the tumorbed. Two randomized trials conducted in Europe haveshown that using boosts of 10 Gy to 16 Gy reduces therisk of local recurrence from 4.6% to 3.6% at 3 years (P= .044),[and from 7.3% to 4.3% at 5 years (P< .0001),

respectively If a boost is used, it can be delivered either by external-

beam radiation therapy,or by using an interstitialradioactive implant.


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Radiation therapy followingmastectomy

Postoperative chest wall and regional lymph node adjuvantirradiation is given to selected patients considered at high risk forlocal-regional failure following mastectomy:

1. Those with 4 or more positive axillary nodes2. Grossly evident extracapsular nodal extension

3. Large primary tumors, and4. Very close or positive deep margins of resection of the primarytumor.

Patients with 1 to 3 involved nodes without any of the previouslynoted risk factors are at low risk of local recurrence, and the value

of routine use of adjuvant radiation therapy is unclear.


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Adjuvant systemic therapy

Hormone therapy

Chemotherapy

Monoclonal antibodies


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Hormone therapy

Tamoxifen

Aromatase inhibitors: anastrozole,exemestane, letrozole

Ovarian ablation


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Tamoxifen

The benefit of tamoxifen was found to be restricted to women withER-positive or ER-unknown breast tumors. In these women, the 15-year absolute reductions in recurrence and mortality associated with5 years of use are 12% and 9%, respectively.

Women younger than 50 years obtained a degree of benefit from 5years of tamoxifen similar to that obtained by older women.

In addition, the proportional reductions in both recurrence andmortality associated with tamoxifen use were similar in women witheither node-negative or node-positive breast cancer, but theabsolute improvement in survival at 10 years was greater in thelatter group (5.3% vs. 12.5% with 5 years of use)

The current recommendation is that adjuvant tamoxifen be

discontinued after 5 years in all patients as current standardtherapy.


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Tamoxifen toxic effects

Endometrial cancer

Increased incidence of deep venousthrombosis and pulmonary emboli.

Benign ovarian cysts

Visual problems


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Aromatase inhibitors:anastrozole

Patients on anastrozole have asignificantly longer disease-free survivalthan those on tamoxifen.


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Aromatase inhibitors:exemestane

Better disease free survival

Women on exemestane had significantly morevisual disturbances, arthralgia, diarrhea, and

osteoporosis, but women on tamoxifen hadsignificantly more gynecologic symptoms,muscle cramps, vaginal bleeding,thromboembolic disease, and second

malignancies other than breast cancer.

No difference was observed in overall survival


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Aromatase inhibitors: letrozole

Better disease free survival

Significantly more hot flashes, arthritis,arthralgia and myalgia, but less vaginalbleeding. New diagnoses of osteoporosiswere more frequent on letrozole

Improvement in overall survival


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Ovarian Ablation

Surgery, radiation therapy or ovariansuppression with LHRH agonists

Ovarian suppression or ablation reducedthe absolute risk of recurrence at 15 yearsby 4.3% and the risk of death from breastcancer by 3.2.


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Chemotherapy

CMF based

Anthracycline based


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Duration of CMF-basedchemotherapy

No survival benefit was demonstrated fordurations greater than 6 months.


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Risk Categories for Women WithNode-Negative Breast Cancer

Low risk(has alllistedfactors)

Intermediate risk

High risk(has atleast 1listed

factor)Tumor size 1cm 1-2 cm >2 cm

ER or PR Status positive positive negative

Tumor grade Grade 1 grade 1-2 grade 2-3


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Adjuvant systemic treatment for


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Adjuvant systemic treatment fornode negative postmenopausal

womenPatientgroup

Low risk Intermediate risk

High risk

ER-positive orPR-positive

None ortamoxifen

TC TC

ER-negative orPR-negative

Chemotherapy

Older than 70

yearsNone ortamoxifen

TC T. Considerchemotherapy ifER-negative or

PR-negative



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Adjuvant systemic treatment fornode positive premenopausal

womenPatient group Treatments

ER or PR-positive 1. C & T2. C & Ov Ab/ GnRH analog

3. C & T & Ov Ab/ GnRH analog

4. Ov ab T

5. GnRH

T

ER-negative or PR-negative Chemotherapy



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Adjuvant systemic treatment fornode positive postmenopausal

womenPatient group Treatments

ER or PR-positive T C

ER-negative or PR-negative Chemotherapy

Older than 70 years Tamoxifen alone; considerchemotherapy if receptor-negative

C did f h dj


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Candidates for whom adjuvanttherapy may not be necessary

Individuals with small primary tumors (


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Inoperable stage IIIB or IIIC orinflammatory breast cancer

Multimodality therapy delivered with curative intent is the standard of carefor patients with clinical stage IIIB disease.

32% of patients with ipsilateral supraclavicular node involvement and noevidence of distant metastases (pN3c) can have prolonged disease-freesurvival at 10 years with combined modality therapy.This result suggestssuch patients should be treated with the same intent.

Initial surgery is generally limited to biopsy to permit the determination ofhistology, ER and PR levels, and HER2/neu overexpression.

Initial treatment with anthracycline-based chemotherapy and/or taxane-based therapy is standard.

For patients who respond to neoadjuvant chemotherapy, local therapy mayconsist of total mastectomy with axillary lymph node dissection followed bypostoperative radiation therapy to the chest wall and regional lymphatics.

Breast-conserving therapy can be considered in patients with a good partialor complete response to neoadjuvant chemotherapy. Subsequent systemictherapy may consist of further chemotherapy.

Hormone therapy should be administered to patients whose tumors are ER-positive or unknown.


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Stage IV breast cancer

Treatment of metastatic breast cancer willusually involve hormone therapy and/orchemotherapy with or without trastuzumab

(Herceptin). Radiation therapy and/or surgerymay be indicated for patients with limitedsymptomatic metastases. Fungating tumours

Bisphosphonates to reduce skeletal morbidity in

patients with bone metastases


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Stage IV breast cancer (cont)

Hormone therapy as initial treatment for a postmenopausal patientwith newly diagnosed metastatic disease if the patients tumor isER-positive, PR-positive, or ER/PR-unknown. Hormone therapy isespecially indicated if the patients disease involves only bone andsoft tissue and the patient has either not received adjuvantantiestrogen therapy or has been off such therapy for more than 1

year. Women whose tumors are ER-positive or unknown, with bone or

soft tissue metastases only, who have received an antiestrogenwithin the past year should be given second-line hormone therapy.Examples of second-line hormone therapy in postmenopausalwomen include selective aromatase inhibitors, such as anastrozole,letrozole, or exemestane; megestrol acetate; estrogens; androgens;and the ER down-regulator, fulvestrant.[


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Stage IV breast cancer (cont)

Premenopausal women should undergo oophorectomy (surgically,with external-beam radiation therapy or with an LHRH agonist).

Patients with lymphangitic pulmonary metastases, major liverinvolvement, and/or central nervous system involvement should notreceive hormone therapy as a single modality. Patients withstructural compromise of weight-bearing bones should be

considered for surgical intervention and/or radiation in addition tosystemic therapy. Patients with vertebral body involvement shouldbe evaluated for impending cord compression even in the absenceof neurologic symptoms. Increasing bone pain and increasingalkaline phosphatase within the first several weeks of hormonetherapy does not necessarily imply disease

Patients whose tumors have progressed on hormone therapy arecandidates for cytotoxic chemotherapy. Patients with hormonereceptor-negative tumors and those with visceral metastases arealso candidates for cytotoxic agents.


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Follow-up

Evidence from randomized trials that periodic follow-upwith bone scans, liver sonography, chest x-rays, andblood tests of liver function does not improve survival orquality of life when compared to routine physicalexaminations.Even when these tests permit earlierdetection of recurrent disease, patient survival isunaffected.

Based on these data, some investigators recommend

that acceptable follow-up be limited to physicalexamination and annual mammography forasymptomatic patients who complete treatment forstage I to stage III breast cancer.

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Treatmentofbreastcancer 110514142146 Phpapp01