Breast Cancer

By Sushila Regmi
Roll no:360
MMC(IOM)
DEFINITION
 Breast cancer is a malignancy originating from breast tissue.
 Disease confined to a localized breast lesion is referred to as early,
primary, localized, or curable.
 Disease detected clinically or radiologically in sites distant from the
breast is referred to as advanced or metastatic breast cancer (MBC),
which is usually incurable.
 EPIDEMIOLOGY
• Two variables most strongly associated with occurrence of breast
cancer are gender and advancing age.
• Additional risk factors include endocrine factors (eg, early men arche,
nulliparity, late age at first birth, and hormone replacement therapy),
genetic factors (eg, personal and family history, mutations of tumor
suppresser genes [BRCA1 and BRCA2]), and environmental and
lifestyle factors (eg, radiation exposure).
• The most common metastatic sites are lymph nodes, skin, bone, liver,
lungs, and brain.
CLINICAL PRESENTATION
• A painless lump is the initial sign of breast cancer in most women. The
typical malignant mass is solitary, unilateral, solid, hard, irregular, and
nonmobile.
• Nipple changes are less commonly seen.
• More advanced cases present with prominent skin edema, redness,
warmth, and induration.
• Symptoms of MBC depend on the site of metastases but may include
bone pain, difficulty breathing, abdominal pain or enlargement,
jaundice, and mental status changes.
DIAGNOSIS
• Initial workup should include a careful history, physical examination
of the breast, three-dimensional mammography, and, possibly, other
breast imaging techniques, such as ultrasound and magnetic
resonance imaging (MRI).
• Breast biopsy is indicated for a mammographic abnormality that
suggests malignancy or for a palpable mass on physical examination
STAGING
• Stage is based on primary tumor extent and size , presence and extent of
lymph node involvement , and presence or absence of distant metastases.
Early Breast Cancer
• Stage 0: Carcinoma in situ or disease that has not invaded the basement
membrane
• Stage I: Small primary invasive tumor without lymph node involvement
• Stage II: Involvement of regional lymph nodes
✓ Locally Advanced Breast Cancer
Stage III: Usually a large tumor with extensive nodal involvement in which the
node or tumor is fixed to the chest wall; also includes inflammatory breast
cancer, which is rapidly progressive
✓ Advanced or Metastatic Breast Cancer
• Stage IV: Metastases in organs distant from the primary tumor
TREATMENT
• Goals of Treatment: Adjuvant therapy for early and locally advanced
breast cancer is administered with curative intent. Treatment of MBC
is done to improve symptoms and quality of life, and to prolong
survival.
EARLY BREAST
CANCER
• Local-Regional Therapy
 Surgery - in situ cancers-
Breast-conserving therapy (BCT)- stage I and II disease-removal of
part of the breast, surgical evaluation of axillary lymph nodes, and
radiation therapy (RT) to prevent local recurrence.
Radiation therapy (RT)- administered to the entire breast over 4 to 6
weeks to eradicate residual disease after BCT.
Systemic Adjuvant Therapy (after
local therapy if no evidence of
metastasis)
• ADJUVANT CHEMOTHERAPY
• Anthracycline-containing regimens (eg, doxorubicin and epirubicin)
reduce the rate of recurrence and death as compared with regimens
that contain cyclophosphamide, methotrexate, and fluorouracil.
• The addition of taxanes, docetaxel and paclitaxel, to adjuvant
regimens resulted in reduced risk of distant recurrence.
• Initiate chemotherapy within 12 weeks of surgical removal of the
primary tumor.
ADJUVANT BIOLOGIC THERAPY
• Trastuzumab in combination with adjuvant chemotherapy is indicated
in patients with early stage, HER2-positive breast cancer. The risk of
recurrence was reduced up to 50% in clinical trials.
ADJUVANT ENDOCRINE THERAPY
• Tamoxifen, toremifene, oophorectomy, ovarian irradiation, luteinizing
hormone releasing hormone (LHRH) agonists, and aromatase inhibitors (AI)
– treatment of primary or early-stage breast cancer.
• Tamoxifen 20 mg daily, beginning soon after completing chemotherapy and
continuing for 5 years, reduces the risk of recurrence and mortality.-
therapy of choice for premenopausal women
• The risks of stroke, pulmonary embolism, deep vein thrombosis, and
endometrial cancer, particularly in women age 50 years or older.
• AIs into adjuvant hormonal therapy for postmenopausal, hormone-
sensitive breast cancer.
• loss/osteoporosis, hot flashes, myalgia/ arthralgia, vaginal dryness/atrophy,
mild headaches, and diarrhea are adverse effect.
LOCALLY ADVANCED BREAST CANCER
(STAGE III)
• primary chemotherapy is the initial treatment of choice
• Primary chemotherapy with an anthracycline- and taxane-containing
regimen is recommended.
• The use of trastuzumab with chemotherapy is appropriate for
patients with HER2-positive tumors.
• Surgery followed by chemotherapy and adjuvant RT should be
administered to minimize local recurrence.
• Cure is the primary goal of therapy for most patients with stage III
disease.
METASTATIC BREAST CANCER
(STAGE IV)
• The choice of therapy for MBC is based on the site of disease
involvement and the presence or absence of certain characteristics.
Endocrine Therapy
• treatment of choice for patients who have hormone receptor–
positive metastases in soft tissue, bone, pleura, or, if asymptomatic,
viscera.
• AIs are generally first line therapy in postmenopausal women. AIs
reduce circulating and target organ estrogens by blocking peripheral
conversion from an androgenic precursor, the primary source of
estrogens in postmenopausal women.
• Tamoxifen, a selective estrogen receptor modulator (SERM) is the
preferred initial agent when metastases are present in
premenopausal women.
• Toremifene, also a SERM, has similar efficacy and tolerability as
tamoxifen and is an alternative to tamoxifen in postmenopausal
patients.
• Fulvestrant is a second-line intramuscular agent with similar efficacy
and safety when compared with anastrozole or exemestane in
patients who progressed on tamoxifen.
• LHRH analogue (goserelin, leuprolide, or triptorelin) is a reversible
alternative to surgery. If used as first-line therapy for MBC,
combination therapy with tamoxifen is recommend.
• Progestins are generally reserved for third-line therapy. They cause
weight gain, fluid retention, and thromboembolic events
Chemotherapy
• Initial therapy for women with hormone receptor–negative tumors;
lung, liver, or bone marrow involvement; and after failure of
endocrine therapy.
• Single agents are associated with lower response rates than
combination therapy.
• Single agents are better tolerated, an important consideration in the
palliative metastatics.
• Treatment with sequential single agents is recommended over
combination regimens unless the patient has rapidly progressive
disease, life-threatening visceral disease, or the need for rapid
symptom control.
Radiation Therapy
• Commonly used to treat painful bone metastases or other localized
sites of disease, including brain and spinal cord lesions. Pain relief is
seen in approximately 90% of patients who receive RT.
Biologic or Targeted Therapy
• anti-HER2 agents-Trastuzumab produces response rates of 15% to
20% when used as a single agent and increases response rates, time
to progression, and OS when combined with chemotherapy.