BREAST CANCER

The most common tumour in women, 216,000 women in the United States are

diagnosed and 40,000 die each year with breast cancer. Men also get breast

cancer at a rate of 150:1. Breast cancer is hormone-dependent. Women with

late menarche, early menopause, and first full-term pregnancy by age 18 have

a significantly reduced risk. The average American woman has about a 1 in 9

lifetime risk of developing breast cancer. Dietary fat is a controversial risk

factor. Oral contraceptives have little, if any, effect on risk and lower the risk

of endometrial and ovarian cancer. Voluntary interruption of pregnancy does

not increase risk. Estrogens replacement therapy may slightly increase the risk,

but the beneficial effects of estrogens on quality of life, bone mineral density,

and decreased risk of colorectal cancer appear to be somewhat outnumbered by

increases in cardiovascular and thrombotic disease. Women who received therapeutic

radiation before age 30 is at increased risk. Breast cancer risk is increased

when a sister and mother also had the disease.

Diagnosis

Breast cancer is usually diagnosed by biopsy of a nodule detected by mammogram

or by palpation. Women should be strongly encouraged to examine

their breasts monthly. In premenopausal women, questionable or nonsuspicious

(small) masses should be re-examined in 2–4 weeks (Fig. 74-1). A mass in a

premenopausal woman that persists throughout her cycle and any mass in a

postmenopausal woman should be aspirated. If the mass is a cyst filled with

non-bloody fluid that goes away with aspiration, the pt is returned to routine

screening. If the cyst aspiration leaves a residual mass or reveals bloody fluid,

the pt should have a mammogram and excisional biopsy. If the mass is solid,

the pt should undergo a mammogram and excisional biopsy. Screening mammograms

performed every other year beginning at age 50 have been shown to

save lives. The controversy regarding screening mammograms beginning at age

40 relates to the following facts: (1) the disease is much less common in the

40- to 49-year age group; screening is generally less successful for less common

problems; (2) workup of mammographic abnormalities in the 40- to 49-year

age group less commonly diagnoses cancer; and (3) about 35% of women who

are screened annually during their forties have an abnormality at some point

that requires a diagnostic procedure (usually a biopsy); yet very few evaluations

reveal cancer. However, many believe in the value of screening mammography

beginning at age 40. After 13–15 years of follow-up, women who start screening

at age 40 have a small survival benefit. Women with familial breast cancer

more often have false-negative mammograms. MRI is a better screening tool in

these women.

Staging

Therapy and prognosis are dictated by stage of disease. Unless the

breast mass is large or fixed to the chest wall, staging of the ipsilateral axilla is

performed at the time of lumpectomy (see below). Within pts of a given stage,

individual characteristics of the tumour may influence prognosis: expression of

estrogens receptor improves prognosis, while overexpression of HER-2/neu, mutations

in p53, high growth fraction, and aneuploidy worsen the prognosis.

Breast cancer can spread almost anywhere but commonly goes to bone, lungs,

liver, soft tissue and brain.

TREATMENT

Treatment varies with stage of disease. Duct carcinoma in situ is non-invasive tumour present in the breast ducts. Treatment of choice is wide excision with breast radiation therapy. In one

study, adjuvant tamoxifen further reduced risk of recurrence.

Invasive breast cancer can be classified as operable, locally advanced, and

metastatic. In operable breast cancer, outcome of primary therapy is the same

with modified radical mastectomy or lumpectomy followed by breast radiation

therapy. Axillary dissection may be replaced with sentinel node biopsy to

evaluate node involvement. The sentinel node is identified by injecting a dye

in the tumour site at surgery; the first node in which dye appears is the sentinel

node. Women with tumours _1 cm and negative axillary nodes require no

additional therapy beyond their primary lumpectomy and breast radiation.

Adjuvant combination chemotherapy for 6 months appears to benefit premenopausal

women with positive lymph nodes, pre- and postmenopausal

women with negative lymph nodes but with large tumours or poor prognostic

features, and postmenopausal women with positive lymph nodes whose tumours

do not express estrogens receptors. Estrogens receptor–positive tumours

_1 cm with or without involvement of lymph nodes are treated with aromatase

inhibitors. Women who began treatment with tamoxifen before aromatase

inhibitors were approved should switch to an aromatase inhibitor after

5 years of tamoxifen.

Adjuvant chemotherapy is added to hormonal therapy in estrogens receptor–

positive, node-positive women and is used without hormonal therapy in

estrogens receptor–negative node-positive women, whether they are pre- or

postmenopausal. Various regimens have been used. The most effective regimen

appears to be four cycles of doxorubicin, 60 mg/m2, plus cyclophosphamide,

600 mg/m2, IV on day 1 of each 3-weekcycle followed by four cycles

of paclitaxel, 175 mg/m2, by 3-h infusion on day 1 of each 3-weekcycle.

The activity of other combinations is being explored. In premenopausal

women, ovarian ablation [e.g., with the luteinizing hormone–releasing hormone

(LHRH) inhibitor goserelin] may be as effective as adjuvant chemotherapy.

Tamoxifen adjuvant therapy (20 mg/d for 5 years) or an aromatase inhibitor

(anastrazole, letrozole, exemestane) is used for pre- or postmenopausal

women with tumours expressing estrogens receptors whose nodes are positive

or whose nodes are negative but with large tumours or poor prognostic features.

50 mg/m2, and 5-fluorouracil 500 mg/m2 all given IV on days 1 and 8 of a

monthly cycle for 6 cycles) followed by surgery plus breast radiation therapy.

Treatment for metastatic disease depends upon estrogens receptor status

and treatment philosophy. No therapy is known to cure pts with metastatic

disease. Randomized trials do not show that the use of high-dose therapy with

hematopoietic stem cell support improves survival. Median survival is about

16 months with conventional treatment: tamoxifen or aromatase inhibitors for

estrogens receptor–positive tumours and combination chemotherapy for receptor-

negative tumours. Pts whose tumours express HER-2/neu have somewhat

higher response rates by adding trastuzumab (anti-HER-2/neu) to chemotherapy.

Some advocate sequential use of active single agents in the setting of

metastatic disease. Active agents in anthracycline- and taxane-resistant disease

include capecitabine, vinorelbine, gemcitabine, irinotecan, and platinum

agents. Pts progressing on adjuvant tamoxifen may benefit from an aromatase

inhibitor such as letrozole or anastrazole. Bisphosphonates reduce skeletal

complications and may promote antitumor effects

By: Ammarah Khan

    

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