Breast CancerBreast Cancer

Dr. Padma Poddutoori,

PG-Y3, I.M.

Dr.Sohail Chaudhry,

Attending Physician, Hemoncology.

Clinical case presentationClinical case presentationCC: lump in the left breastHOPI: A 47 yr old premenopausal woman

who was doing well until 8 months back when she first noticed a lump in the left breast at 2 ‘O’ clock position. A diagnostic mammogram showed 2 nodular densities in the left upper quadrant, close to the palpable abnormality. U/S showed a cluster of cysts in between the 12 and 1 ‘O’ clock position and a thick walled cyst, in between 11 and 12 ‘O’ clock position, 1.8 cm from which greenish black fluid was aspirated.

Clinical case presentation Clinical case presentation contd…contd…

An U/S which was done 3 wks later, which showed a suspicious solid mass.

Core needle biopsy done showed grade 2 invasive ductal carcinoma in 4 of 4 cores, ER and PR positive, no over expression of HER2/neu.

Menstrual and gynecologic history: She was nulliparous with menarche at 13, was exposed to

DES, no h/o OCP use and had undergone routine gynecologic screening

Vaginal biopsy 23 yrs back showed adenosis with no evidence of cancer

Clinical case presentationClinical case presentation contd… contd…

Allergies: stinging insectsPMH: no h/o DM, HTN or CADSocial history: lives with her husband, non

smoker, drinks fewer than 5 alcoholic beverages a wk.

Family history: no h/o breast or ovarian cancer

Medications: none

Clinical case presentation Clinical case presentation contd…contd…

Vitals: normal On examination:

Breast: breasts were symmetric, no skin changes, nipple discharge or erosions. A flat mass 5x 5 cms was palpated in the upper outer quadrant left breast, not mobile, not attached to overlying skin, no lymphadenopathy, no mass in the right breast.

Rest of the examination was normal

Imaging Imaging Radionuclide bone scan showed a focus of increased uptake

in the right aspect of the T6 vertebral body, which suggested the possibility of a metastasis.

Mammography revealed an ill defined mass in the upper outer quadrant of the left breast.

A targeted ultrasonography of the left breast revealed an ill-defined, hypoechoic, lobulated mass, 3.5 cm by 2.7 cm x 2.0 cm, at 2 o’clock position.

MRI of the breasts revealed an ill-defined, lobulated, enhancing mass, 2.9 cm x 2.7 cm x 2.5 cm, in the upper outer quadrant of left breast, corresponding to the mammographic and ultrasonographic findings.

CT of the thoracic spine, performed revealed a lytic destructive lesion, 1.8 cm x 1.6 cm x 1.5 cm, in the right side of T6 vertebral body. A small, soft-tissue component extended into the right anterior lateral epidural space, without central canal stenosis.

Needle biopsy of the T6 vertebral lesion was performed under CT guidance, and pathological examination showed metastatic carcinoma.

Gradishar W et al. N Engl J Med 2008;359:1382-1391

Breast Imaging Studies

Gradishar W et al. N Engl J Med 2008;359:1382-1391

Spine Lesion Imaging Study

Pathology Pathology

All four tissue cores had involvement by both infiltrating ductal Ca and ductal CIS, with focally abundant extracellular mucin.

Immunohistochemical staining showed the expression of both ER and PR.

Breast cancer incidenceBreast cancer incidence It is the most common malignancy in women-31% of all

female cancers, 15% of cancer deaths-no 2 cause of cancer deaths

178,480 new invasive breast cancer cases were diagnosed in women in U.S in 2007

Epidemiology: Gender: female:male =100:1; BRCA mutations are

associated with increased risk for br.cancer in men Age: 0.8% in women <30 yrs old, 6.5% in women 30-40 yrs

old Race: Caucasians > African Americans Geography: north america highest rate in the world SES: higher in higher SES Disease site: left >right and higher in the UOQ and in

retroareolar area

Basic principles of treatment Basic principles of treatment of breast cancerof breast cancer

Local and Regional Treatment Early breast cancer: lumpectomy with RT. Axillary Lymph-Node Dissection:

recurrence is higher in women with positive axillary LN. Sentinel LN mapping can be done, which has 100% PPV and 95% NPV

Radiotherapy: RT is an integral part of breast-conserving treatment.

Postmastectomy RT reduces the incidence of local and regional recurrences by 50 to 75%.

Basic principles of treatment Basic principles of treatment of breast cancerof breast cancer

Systemic Hormone Therapy or Chemotherapy: For adjuvant therapy, combination CT is more effective than single-drug therapy, reducing the annual risk of death by 20%. The benefit is greater when tamoxifen is given for 5 yrs, and with ER positive tumors.

Preoperative Chemotherapy: 90% of primary operable tumors decrease in size by >50% after CT, thus making lumpectomy a possibility for women who would otherwise have required a mastectomy. No survival benefit of pre-op CT over post-op CT

Duration of Chemotherapy: 4-6 M. The combinations used most often are fluorouracil, doxorubicin, and cyclophosphamide (FAC); fluorouracil, epirubicin, and cyclophosphamide (FEC); doxorubicin and cyclophosphamide (AC); and cyclophosphamide, methotrexate, and fluorouracil (CMF). These combinations are given at intervals of 3-4 wks. 6 cycles of FAC or FEC (18 to 24 wks), 6 cycles of CMF (18 to 24 wks), or 4 cycles of AC (12 to 16 wks) are considered standard therapy.

In premenopausal women, ovarian ablation has a benefit, equal to that of combn CT or tamoxifen.

Combination CT and Hormonal Therapy: more effective than either alone. Recommended for women with a high risk of recurrent disease.

Metastatic Breast Cancer: optimal palliation and prolongation of life are the main goals of treatment.

INDICATIONS FOR ADJUVANT SYSTEMIC THERAPY AFTER INDICATIONS FOR ADJUVANT SYSTEMIC THERAPY AFTER SURGERY IN WOMENSURGERY IN WOMEN

WITH OPERABLE BREAST CANCER.WITH OPERABLE BREAST CANCER.

TYPE OF DISEASE ADJUVANTTHERAPY INDICATED

Breast cancer without evidence of invasionNoninvasive breast cancer (ductal or lobular carcinoma in situ)Breast cancer with evidence of invasion, but -ve axillary LNMicroinvasive breast cancer (<1 mm in largest diameter)Invasive ductal or lobular carcinoma <1 cm in largest diameterInvasive carcinoma <3 cm in largest diameter with favorablehistologic findings (pure tubular, mucinous, or papillary)Invasive ductal or lobular carcinoma »1 cm in largestdiameter

Invasive carcinoma »3 cm in largest diameter with favorablehistologic findings (pure tubular, mucinous, or papillary)

Invasive breast cancer with positive axillary lymph nodesAll tumors, regardless of size or histologic findings

None

NoneNoneNone

Chemotherapy, hormonaltherapy, or bothChemotherapy, hormonaltherapy, or bothChemotherapy, hormonaltherapy, or both

SELECTION OF ADJUVANT SYSTEMIC THERAPY FOR WOMEN WITH OPERABLE PRIMARY BREAST CANCER AND INDICATIONS FOR ADJUVANT

TREATMENT.CHARACTERISTICS OF PATIENT AND TUMOR LEVEL OF RISK ADJUVANT SYSTEMIC THERAPY*AGEESTROGEN-RECEPTORSTATUS

LEVEL OF RISK ADJUVANT SYSTEMIC THERAPY

<50 yr NegativePositive

Positive

Unknown»50 yr NegativePositivePositive

Unknown

AnyLow

Moderate or high

Any

AnyLowModerate or high

Any

ChemotherapyHormonal therapyOr Chemotherapy or Chemotherapy and hormonal therapyChemotherapy and hormonal therapy or Investigational therapies

Chemotherapy and hormonal therapy

ChemotherapyTamoxifen Or Chemotherapy and hormonal therapyChemotherapy and hormonal therapy or Investigational therapies

Chemotherapy and hormonal therapy

TEN-YEAR CANCER-FREE SURVIVAL AND OVERALL TEN-YEAR CANCER-FREE SURVIVAL AND OVERALL SURVIVAL AMONG WOMEN TREATED WITH SURVIVAL AMONG WOMEN TREATED WITH

CHEMOTHERAPY WITH OR WITHOUT RADIOTHERAPY CHEMOTHERAPY WITH OR WITHOUT RADIOTHERAPY

AFTER MASTECTOMYAFTER MASTECTOMY..STUDYANDOUTCOME

NO. OFSUBJECTS

PERCENT SURVIVING CHEMOTHERAPYCHEMOTHERAPYANDRADIOTHERAPY

PVALUE

British ColumbiaCancer-free survivalOverall survivalDanish Breast CancerCooperative GroupCancer-free survivalOverall survival

318

1708

41 5654 64

34 4845 54

0.0070.07

<0.001<0.001

Hortobagyi G. N Engl J Med 1998;339:974-984

Optimal Palliative Therapy for Women with Metastatic Breast Cancer

Hormonal therapyHormonal therapy Pre-menopausal women:

Tamoxifen x 5 yrs

AI[Arimidex or Famara] with LHRH agonist +/- zometa ?

A study was conducted in premenopausal women- 2 groups enrolled:

Tamoxifen +LHRH agonist +/- Zometa

vs

AI + LHRH agonist +/- Zometa

Post menopausal women:

Tamoxifen x 5 yrs

AI[Arimidex or Famara] x 5 yrs

Tamoxifen x 5 yrs Famara x 5 yrs

Tamoxifen x 2.5 yrs Aromasin [Exemestane]

HORMONAL THERAPIES FOR WOMEN WITH HORMONAL THERAPIES FOR WOMEN WITH METASTATIC BREAST CANCERMETASTATIC BREAST CANCER

ORDER OFTHERAPY

PREMENOPAUSAL WOMEN POSTMENOPAUSAL WOMEN

First line Antiestrogens or ovarian ablation(chemical, surgical, or postradiation)

Antiestrogens

Second line Ovarian ablation after antiestrogens;antiestrogens after ovarianablation

Aromatase inhibitors

Third line Progestins Progestins

Fourth line Androgens Androgens or estrogens

Newer modalities of treatmentNewer modalities of treatment Bevacizumab (Avastin, Genentech) is a

humanized monoclonal antibody directed against all isoforms of VEGF-A.

Trastuzumab, a monoclonal antibody targeting the extracellular domain of the HER2 protein, was approved in 1998 as a first-line treatment in combination with paclitaxel for HER2-positive metastatic breast cancer.

Exemestane[Aromasin] inhibits aromatization in vivo by about 98 %. Exemestane therapy after 2-3 yrs of tamoxifen therapy significantly improved disease-free survival as compared with the standard 5 yrs of tamoxifen treatment.

Analyses of Toxic Effects and Efficacy

Miller K et al. N Engl J Med 2007;357:2666-2676

Demographic and Disease Characteristics of Eligible Patients

Miller K et al. N Engl J Med 2007;357:2666-2676

Survival Analyses

Romond E et al. N Engl J Med 2005;353:1673-1684

Enrollment, Patients, and the Timing of Chemotherapy and Trastuzumab in Trial B-31 and Trial N9831

Romond E et al. N Engl J Med 2005;353:1673-1684

Kaplan-Meier Estimates of Disease-free Survival (Panel A) and Overall Survival (Panel B)

What can beWhat can be done in this patient? done in this patient?

THANK YOU!THANK YOU!