Breast Cancer

Breast cancer is the common term for a set of breast tumor subtypes with distinct molecular and cellular origins and clinical behavior. Most of these are epithelial tumors of ductal or lobular origin (see the image below). Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the leading cause of cancer death among women.

Signs and symptoms

Early breast cancers may be asymptomatic, and pain and discomfort are typically not present. If a lump is discovered, the following may indicate the possible presence of breast cancer:

• Change in breast size or shape, even if no lump is palpable ^[1]
• Skin dimpling or skin changes
• Recent nipple inversion or skin change, or nipple abnormalities
• Single-duct discharge, particularly if blood-stained
• Axillary lump

Diagnosis of breast cancer

Breast cancer is often first detected as an abnormality on a mammogram before it is felt by the patient or health care provider.

Evaluation of breast cancer includes the following:

• Clinical examination
• Imaging
• Needle biopsy

Physical examination

The following physical findings should raise concern:

• Lump or contour change
• Skin tethering
• Nipple inversion
• Dilated veins
• Ulceration
• Eczemalike rash or redness on the nipple or the surrounding area
• Nipple discharge
• Edema or peau d’orange

If a palpable lump is found and possesses any of the following features, breast cancer may be present:

• Hardness
• Irregularity
• Focal nodularity
• Fixation to skin or muscle

Screening

Early detection remains the primary defense in preventing advanced breast cancer. Screening modalities include the following:

• Mammography with tomosynthesis ^[2]
• Ultrasonography
• Magnetic resonance imaging (MRI) with and without contrast

Ultrasonography and MRI are more sensitive than mammography for invasive cancer in nonfatty breasts. Combined mammography, clinical examination, and MRI are more sensitive than any other individual test or combination of tests.

Breast self-examination is no longer recommended. Instead, breast awareness is recommended; women should be familiar with how their breasts normally look and feel, and report any changes promptly to their health care provider. ^{[2, 3]} Most guidelines also recommend against clinical breast examination for screening. ^{[4, 5]}

Biopsy

Core biopsy with image guidance is the recommended diagnostic approach for newly diagnosed breast cancers. This obtains breast tissue without surgery and can eliminate the need for additional surgeries. Open excisional biopsy is the surgical removal of the entire lump.

Management of breast cancer

Surgery, radiation therapy, and adjuvant hormone or chemotherapy when indicated are considered primary treatment. Surgical therapy may consist of lumpectomy or total mastectomy with sentinel lymph node biopsy (SLNB) or complete axillary lymph node dissection (ALND). Radiation therapy may follow surgery in an effort to eradicate residual disease while reducing recurrence rates. Adjuvant systemic therapies (eg, hormonal therapy, chemotherapy, targeted therapies), when indicated, are recommended on the basis of tumor biology, stage, and gene expression assay results, as well as individual patient factors such as comorbidities and personal preferences.

Pharmacologic agents

Pharmacologic treatment for breast cancer is typically selected according to the molecular characteristics of the tumor and the disease stage. Agents used (alone or in combination) include the following ^[6] :

• Hormone therapy (eg, tamoxifen, aromatase inhibitors)
• HER2-targeted therapy (monoclonal antibodies [eg, trastuzumab, pertuzumab]; antibody-drug conjugates [eg, ado-trastuzumab emtansine, trastuzumab deruxtecan); tyrosine kinase inhibitors [eg, tucatinib, neratinib])
• CDK4/6 inhibitors (eg, palbociclib, ribociclib, abemaciclib)
• mTOR inhibitors (everolimus)
• PIK3CA inhibitors (alpelisib)
• AKT inhibitor (capivasertib)
• Chemotherapy (eg, cyclophosphamide, doxorubicin, carboplatin, methotrexate)
• PARP inhibitors for germline BRCA1 and BRCA2 mutations (eg, olaparib, talazoparib)
• Immunotherapy (pembrolizumab)

In patients receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture, the monoclonal antibody denosumab or either of the bisphosphonates zoledronic acid and pamidronate may be added to the treatment regimen to increase bone mass. These agents are given along with calcium and vitamin D supplementation.