Breast Cancer, Female

Essentials of Diagnosis

• Risk factors

  • Age

  • Nulliparity

  • Childbirth after age 30

  • Family history of breast cancer or genetic mutations (BRCA1, BRCA2 or others)

  • Personal history of breast cancer or some types of proliferative conditions

• 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

• A woman's risk of breast cancer rises rapidly until her early 60s, peaks in her 70s, and then declines

• A significant family history of breast or ovarian cancer may also indicate a high risk of developing breast cancer

• Germline mutations in the BRCA family of tumor suppressor genes or other breast cancer susceptibility genes account for approximately 5–10% of breast cancer diagnoses and tend to cluster in certain ethnic groups, including women of Ashkenazi Jewish descent

• Women with a mutation in the BRCA1 gene, located on chromosome 17, have an estimated 85% chance of developing breast cancer in their lifetime

• Other genes associated with an increased risk of breast and other cancers include

  • BRCA2 (associated with a gene on chromosome 13)

  • Ataxia-telangiectasia mutation (ATM), BARD1, CHEK2, PALB2, RAD51D

  • Mutation of the tumor suppressor gene p53

• Primary care clinicians should assess a woman's personal and family history for breast, ovarian, tubal or peritoneal cancer using a familial risk assessment tool

• Those with a positive result should receive genetic counseling in order to decide whether genetic testing is indicated

Demographics

• Second most common cancer in women

• Second most common cause of cancer death in women

• 268,000 new cases and 41,760 deaths from breast cancer in US women in 2019

• 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 deleterious 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