Breast Cancer, Female

For further information, see CMDT Part 17-07: Carcinoma of the Female Breast

Essentials of Diagnosis

• Early findings

  • No palpable mass, or

  • Single, nontender, firm to hard mass with ill-defined margins

  • Mammographic abnormalities

• Later findings

  • Breast mass, enlargement, redness, edema, pain

  • Skin or nipple retraction

  • Fixation of mass to skin or chest wall

  • Axillary lymphadenopathy

General Considerations

• Risk of breast cancer

  • Rises rapidly with advancing age until early 60s, peaks in 70s, and then declines

  • Is doubled in those who have one first-degree relative diagnosed with breast cancer

  • Is tripled in those with two first-degree relatives diagnosed with breast cancer

  • Is further increased if disease in affected family member is bilateral or diagnosed before menopause

  • Is increased in nulliparous women and women whose first full-term pregnancy occurred after the age of 30

  • Is increased if menarche begins at age < 12 or natural menopause occurs at age > 55, especially for hormone receptor–positive breast cancer

  • Increased risk if history of uterine cancer

  • Appears to increase with use of combined oral contraceptive pills; longer use is associated with higher risk

  • May also increase with alcohol consumption, high dietary intake of fat and lack of exercise

• Increased incidence of breast cancer with fibrocystic disease

  • On biopsy

    • Proliferative changes

    • Papillomatosis

    • Atypical epithelial hyperplasia

  • On mammogram

    • Increased breast density

• Contralateral cancer develops in women with prior breast cancer at a rate of 1–2% per year

• Risk of breast cancer with gene mutations

  • Estimated 85% lifetime risk in women with BRCA1 gene mutations

  • Increased risk with BRCA2, ataxia-telangiectasia, and p53 gene mutations

  • Other mutations have been identified that increase the risk of breast cancer but have significantly lower risk than BRCA mutations

Demographics

• Second most common cancer in women

• Second most common cause of cancer death in women

• 268,670 new cases and 41,400 deaths from breast cancer in US women in 2018

• Worldwide, breast cancer is diagnosed in approximately 2.1 million women, and about 626,679 die of breast cancer each year

Symptoms and Signs

• Presenting complaint is a lump (usually painless) in 70%

• Less frequently

  • Breast pain

  • Nipple discharge

  • Erosion, retraction, enlargement, or itching of the nipple

  • Redness, generalized hardness, enlargement, or shrinking of the breast

  • Axillary mass or swelling of the arm (rare)

• With metastatic disease, back or bone pain, jaundice, or weight loss

• Physical examination is done with patient sitting, arms at sides and then overhead, and supine with arm abducted

• Findings include

  • Nontender, firm or hard mass with poorly delineated margins

  • Skin or nipple retraction or dimpling

  • Breast asymmetry

  • Erosions of nipple epithelium

  • Watery, serous or bloody discharge

• Metastatic disease suggested by

  • Firm or hard axillary nodes > 1 cm

  • Axillary nodes that are matted or fixed to skin or deep structures indicate advanced disease (at least stage III)

• Advanced stage (stage III or IV) cancer suggested by ipsilateral supraclavicular or infraclavicular nodes

Differential Diagnosis

• Fibrocystic condition of breast

• Fibroadenoma

• Intraductal papilloma

• Lipoma

• Fat necrosis

Laboratory Tests

• Alkaline phosphatase increased with liver or bone metastases

• Serum calcium elevated in advanced disease

• Serum tumor markers such as carcinoembryonic antigen (CEA) and CA 15-3 or CA 27-29 are not recommended for diagnosis of early lesions nor for routine surveillance for recurrence after a breast cancer diagnosis

Imaging Studies

• Mammography

• Tomosynthesis

  • Creates tomographic “slices” of the breast volume with a single acquisition

  • May improve the sensitivity of mammogram especially in patients with dense breast tissue

  • Has not yet been shown to improve patient outcomes in prospective studies

• Breast ultrasound may differentiate cystic from solid masses

• MRI

  • The sensitivity of MRI is much higher than mammography

  • However, the specificity is significantly lower, and this results in multiple unnecessary biopsies

  • The National Comprehensive Cancer Network guidelines recommend MRI in addition to screening mammography for high-risk women, including those

    • With BRCA1/2 mutations

    • Who have a lifetime risk of breast cancer of at least 20%

    • With a personal history of lobular carcinoma in situ

• Chest imaging with CT or radiographs may be done to evaluate for pulmonary metastases

• Abdominal imaging with CT or ultrasound may be done to evaluate for liver metastases

• Bone scan may show bony metastases in symptomatic patients

• PET scanning alone or combined with CT may also be used for detecting soft tissue or visceral metastases in patients with symptoms or signs of metastatic disease

Diagnostic Procedures

• Fine-needle aspiration (FNA) or core biopsy

• Open biopsy under local anesthesia if needle biopsy inconclusive

• Computerized stereotactic or ultrasound guided core needle biopsies for nonpalpable lesions found on mammogram

• TNM staging (I–IV)

• Cytologic examination of breast nipple discharge may be helpful on rare occasions

• Most patients with early breast cancer can be cured

• Treatment with a curative intent is advised for clinical stage I, II, and III disease (Table 39–2)

• Patients with locally advanced (T3, T4) and even inflammatory tumors may be cured with multimodality therapy

• See Table 17–5 for hormonal agents commonly used to manage metastatic breast cancer

• Palliative care

  • Appropriate for all patients with stage IV disease and for patients with unresectable local cancers

  • Aimed at managing symptoms, improving quality of life, and even prolonging survival, without the expectation of achieving cure

Follow-Up

• Examine patient every 6 months for the first 2 years after diagnosis; thereafter, annually

Complications

• Pleural effusion occurs in almost half of patients with metastatic breast cancer

• Local recurrence occurs in 8%

• Significant edema of the arm occurs in about 10–30%; more commonly if radiotherapy to axilla after surgery

Prognosis

• Stage of breast cancer is the most reliable indicator of survival rate

  • TNM stage 0: 95% at 5 years; 90% at 10 years

  • TNM stage I: 85% at 5 years; 70% at 10 years

  • TNM stage IIA: 70% at 5 years; 50% at 10 years

  • TNM stage IIB: 60% at 5 years; 40% at 10 years

  • TNM stage IIIA: 55% at 5 years; 30% at 10 years

  • TNM stage IIIB: 30% at 5 years; 20% at 10 years

  • TNM stage IV: 5–10% at 5 years; 2% at 10 years

  • All: 65% at 5 years; 30% at 10 years

• Clinical cure rate of localized invasive breast cancer treated with most accepted methods of therapy is 75% to > 90%

• When axillary lymph nodes are involved, the survival rate drops to 50–70% at 5 years and 25–40% at 10 years

• Estrogen and progesterone receptor-positive primary tumors have a more favorable course

• Table 17–4 lists prognostic factors in node-negative breast cancer

Prevention

• American College of Radiology, American Medical Association, and National Comprehensive Cancer Network (NCCN) recommend annual mammography screening for women aged 40 and older

• US Preventive Services Task Force (USPSTF) recommends starting screening at age 50

• Most guidelines recommend annual screening

  • However, the American Cancer Society recommends decreasing the frequency of screening to every 1–2 years starting at age 55 years old

  • The USPSTF recommends routine mammography be done no more than every 2 years beginning at age 50

• It is generally agreed that mammography should continue until life expectancy is shorter than 7–10 years, though the USPSTF recommends stopping screening after age 74 years old regardless of life expectancy

When to Refer

• Women with exceptional family histories should be referred for genetic counseling and testing

When to Admit

• For definitive therapy by lumpectomy, axillary node dissection or sentinel node biopsy, or mastectomy after diagnosis by FNA or core needle biopsy

• For complications of metastatic disease