Breast Cancer

Descriptive text is not available for this image BASICS

Most commonly diagnosed cancer (CA) in women and the second most common cause of CA death for U.S. women; females have a ~13% chance of developing breast cancer (BC) and a 2.5% chance of dying from BC if they develop the disease.

DESCRIPTION

  • Malignant neoplasm of cells native to the breast—epithelial, glandular, or stroma
  • Types: invasive (infiltrating ductal carcinoma, infiltrating lobular carcinoma) or noninvasive (ductal carcinoma in situ [DCIS])
  • Molecular subtypes: luminal A (ER+/PR+/HER2−), triple negative (ER−/PR−/HER2−), luminal B (ER+/HER−), luminal B-like (ER+/HER2+), HER2-enriched (ER−/PR−/HER2+)

EPIDEMIOLOGY

Incidence

Estimated in 2024: ~310,720 new cases of invasive BC, ~56,500 DCIS; ~42,250 deaths from BC in U.S. women; increased by ~0.5% per year since mid-2000s

Prevalence

>4 million BC survivors in the U.S. (1)

ETIOLOGY AND PATHOPHYSIOLOGY

Genes such as BRCA1 and BRCA2 function as tumor suppressor genes, and mutation leads to cell cycle progression and limitations in DNA repair. Mutations in estrogen/progesterone induce cyclin D1 and c-Myc expression, leading to cell cycle progression. Additional tumors (33%) may cross talk with estrogen receptors and epidermal growth factor receptors (EGFR), leading to similar abnormal cellular replication.

Genetics

  • Criteria for additional risk evaluation/gene testing in affected BC individual
    • BC at aged ≤50 years
    • BC at any age and
      • ≥1 family member with BC (≤50 years of age or in men) or ovarian/fallopian tube/primary peritoneal CA any age
      • ≥2 family members with BC or pancreatic CA any age
      • Population at increased risk (e.g., Ashkenazi Jewish descent)
    • Triple-negative BC (ER−, PR−, HER2−)
    • Second primary BC (not recurrence of first), ovarian/fallopian tube/primary peritoneal CA
    • ≥1 family member with BC and CA of thyroid, adrenal cortex, endometrium, pancreas, central nervous system, diffuse gastric, aggressive prostate (Gleason score of >7), leukemia, lymphoma, sarcoma, dermatologic manifestations, and/or macrocephaly, gastrointestinal (GI) hamartomas
    • Male BC
  • 5–10% of BCs are associated with genetic mutations and are thus hereditary.
    • BRCA1 and BRCA2 are inherited in an autosomal fashion and have increased risk of BC, ovarian CA, pancreatic CA, and possibly other CAs.
    • Syndromes associated with BC: Cowden syndrome (PTEN), Li-Fraumeni syndrome (TP53), ataxia-telangiectasia (ATM), and Peutz-Jeghers (STK11), hereditary diffuse gastric CA (CDH1); other BC genes include PALB2 and CHEK2.

RISK FACTORS

  • National Cancer Institute Breast Cancer Risk Assessment Calculator: https://bcrisktool.cancer.gov
  • Nonmodifiable risk factors
    • Female sex, aged >65 years, tall stature, dense breasts (>50%), Ashkenazi Jewish descent
    • Biopsy confirmed atypical hyperplasia, DCIS, lobular carcinoma in situ (LCIS)
    • Hereditary BC susceptibility genes
    • Personal or family history of BC at a younger age, history of endometrial or ovarian CA, history of radiation or diethylstilbestrol (DES) exposure (especially at a young age)
    • Hormonal factors: early menarche (<12 years of age), late menopause (>55 years of age), first pregnancy at >35 years of age, postmenopausal
  • Modifiable risk factors
    • Obesity
    • Alcohol use
    • Hormone replacement therapy (combination estrogen-progesterone and estrogen only agents [but not vaginal estrogen]) during perimenopause increases BC risk for 10 years after medication is discontinued.
    • Nulliparous, no history of full-term pregnancy or breastfeeding

GENERAL PREVENTION

  • Medication: United States Preventative Services Task Force (USPSTF) recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors (AIs), to women >35 years old who have a >3% risk for BC and low risk for adverse medication effects (B grade recommendation).
  • Clinical breast exam (CBE): USPSTF: insufficient evidence to assess clinical benefits and harms; American Cancer Society (ACS): no clear benefit Breast self-exams are no longer recommended.
  • Mammography (MMG):
    • USPSTF: Women should undergo biennial mammogram starting at aged 40 years until aged 74 years (B grade recommendation).
    • ACS: Women annual mammograms starting at aged 45 to 54 years, then women >55 years of age biennial mammograms or yearly screening if desired (1); aged 40 to 44 years, optional mammograms yearly

COMMONLY ASSOCIATED CONDITIONS

History of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and LCIS

Descriptive text is not available for this image DIAGNOSIS

HISTORY

  • Painless lump in breast or axilla; swelling, thickening, redness, or dimpling of the skin
  • Breast or nipple pain or nipple discharge (serous, serosanguineous, or bloody), erosion, or retraction

PHYSICAL EXAM

  • Visualize breasts sitting and supine looking for skin dimpling, peau d’orange, and asymmetry.
  • Palpation of all four breast quadrants and regional lymph node exam: cervical, supraclavicular, infraclavicular, axillary

DIFFERENTIAL DIAGNOSIS

  • Benign breast disease:
    • Fibrocystic disease, fibroadenoma
    • Intraductal papilloma (bloody nipple discharge), duct ectasia
    • Simple cyst, galactocele
    • Sclerosing adenosis, fat necrosis (history of serial/parallel breast trauma)
  • Infection: abscess, cellulitis, mastitis

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • MMG Breast Imaging–Reporting and Data System (BI-RADS): BI-RADS is a quality assurance (QA) method published by the American College of Radiology Society.
    • BI-RADS has been extended to breast US and MRI interpretation as well.
    • Components of BI-RADS report: Overall breast composition, including breast density, which is graded from almost entirely fatty tissue to extremely dense.
  • Final BI-RADS assessment category:
    • BI-RADS 0: incomplete; additional imaging evaluation needed and/or prior imaging for comparison
    • BI-RADS 1: negative; continue with current screening guidelines
    • BI-RADS 2: benign; no further action needed
    • BI-RADS 3: probably benign; possibility of malignancy is ≤2%.
    • BI-RADS 4: Suspicious—patient and clinician should discuss possible biopsy.
    • BI-RADS 5: highly suggestive of malignancy, possibility of malignancy ≥95%
    • BI-RADS 6: known biopsy—proven malignancy
  • Calcifications on screening MMG requires diagnostic mammogram (Dx MMG) and stereotactic-guided biopsy.
  • Palpable masses on exam should be evaluated with Dx MMG and US ± biopsy.
    • Palpable mass ≥30 years of age: Obtain Dx MMG and US to determine cystic versus solid. If BI-RADS 1 to 3, then get US ± biopsy. If BI-RADS 4 to 6, then get core needle biopsy ± surgical excision.
  • Palpable mass <30 years of age: Obtain US ± Dx MMG ± biopsy; if low clinical suspicion, observe for 1 to 2 menstrual cycles for resolution.
  • Spontaneous, reproducible nipple discharge: Obtain Dx MMG ± US; if negative, consider ductogram or MRI ± surgical excision.
  • Asymmetric thickening/nodularity: <30 years of age: Obtain US ± Dx MMG ± biopsy; ≥30 years of age: Obtain Dx MMG+ US ± biopsy.
  • Skin changes, peau d’orange: Obtain Dx MMG ± US ± biopsy for underlying mass; if no mass, then perform punch biopsy of skin change.
  • Palpable lymph nodes: Obtain CT scan of chest, abdomen/pelvis, and bone scan.
  • All newly diagnosed BC should be offered multidisciplinary care including genetic and fertility counseling.

Follow-Up Tests & Special Considerations

  • Advanced disease (stage IIIA or higher): chest CT, abdominal ± pelvis CT, FDG positron emission tomography (PET)/CT scan, bone scan, or sodium fluoride PET/CT if FDG-PET/CT indeterminate
  • Breast MRI if indeterminant BC (particularly in dense breasts), invasive BC not captured on mammographic projections, and for surgical planning
  • Most common metastasis: lungs, liver, bone, brain
  • Bone scan if localized bone pain or elevated alkaline phosphate
  • Abdominal ± pelvis CT if abdominal symptoms, elevated alkaline phosphate, abnormal LFTs
  • Chest CT if pulmonary symptoms present
  • Brain/spine MRI if CNS/spinal cord symptoms

Diagnostic Procedures/Other

  • Primary tumor: fine-needle aspiration (FNA), US-guided core needle biopsy, stereotactic-guided core-needle biopsy, MRI-guided biopsies for abnormalities only visualized on breast MRI
  • US of axillary lymph nodes during work-up and core-needle biopsy or FNA if suspicious nodes are identified.

Descriptive text is not available for this image TREATMENT

MEDICATION

  • Neoadjuvant chemotherapy: locally advanced (large tumor and/or positive lymph nodes), early operable BC to facilitate breast conservation surgery, triple negative BC and tumor size >0.5 cm, HER2 (+) tumors ≥2 cm with positive lymph nodes
  • Consider 21-gene PT-PCR assay (Oncotype DX) in ER/PR(+) tumors with (−) nodes to potentially assess risk of recurrence; not validated to predict chemotherapy response; can determine if chemotherapy indicated in the adjuvant setting
  • Cytotoxic therapy: anthracyclines, taxanes, alkylating agents, antimetabolites; higher risk patients with nonmetastatic operable tumors, patients with high risk of recurrence after local treatment (status post surgery ± radiation)
  • Dose-dense chemotherapy demonstrates overall survival advantage in early BC: doxorubicin/cyclophosphamide (AC) weekly or every 2 weeks paclitaxel for HER2 negative BC
  • Anti-HER2/neu antibody (e.g., trastuzumab with or without pertuzumab) in HER2/neu-positive patients; given with other chemotherapy agents in the neoadjuvant or adjuvant setting
  • PD-1 inhibitors like pembrolizumab for triple negative BC in neoadjuvant setting or in metastatic disease if PD-L1>10%

ADDITIONAL THERAPIES

  • External beam radiation therapy (EBRT) is the most common type of radiation for treating BC.
    • After a mastectomy if tumor is >5 cm, ≥1 lymph nodes are involved, chest wall/skin involvement or unable to obtain clear margins
    • After breast-conserving surgery radiation: whole breast radiation, prior to starting endocrine therapy
  • Whole breast radiation: 5 days a week for 6 to 7 weeks.
  • General prevention for high-risk lesions (LCIS, ALH, ADH); tamoxifen 20 mg QD for 5 years, or low dose tamoxifen 10 mg every other day for 3 years
  • Hormone therapy for ER+ tumors
    • DCIS: tamoxifen 200 mg QD for 5 years
      • In postmenopausal women, use of AIs are as effective.
    • Invasive CA:
      • SERM (tamoxifen): premenopausal at diagnosis: 5-year treatment and consider for additional 5 years; avoid during lactation, pregnancy, or with history of deep venous thrombosis/pulmonary embolism.
      • AIs (anastrozole, letrozole, exemestane): postmenopausal women, 5-year treatment following endocrine therapy, or endocrine therapy for up to 10 years
      • Ovarian ablation or suppression with luteinizing hormone–releasing hormone agonists: premenopausal women
  • Advanced disease: hormone and cytotoxic therapy, bisphosphonates, CD4/6 inhibitors, anti-HER2/neu antibody in select HER2/neu-positive patients

Pregnancy Considerations

  • Mastectomy or breast conservation: BCT can be offered at any point in pregnancy, but may require delay in adjuvant RT with sentinel lymph node biopsy (SLNB).
  • Lymphoscintigraphy is safe in pregnancy with radioactive colloid alone
  • Chemotherapy: appropriate in 2nd and 3rd trimesters; trastuzumab contraindicated; RT: Avoid until after delivery.

SURGERY/OTHER PROCEDURES

  • Breast-conserving surgery (lumpectomy, partial mastectomy, segmental mastectomy) removes the cancerous cells and some surrounding tissue while preserving the rest of the breast.
  • Mastectomy: entire breast including some nearby tissues are removed (indicated for multicentric disease, large tumor to breast size ratio, inflammatory BC, T4 disease, contraindication to RT, and/or patient preference)
  • Axillary nodes: preoperative US and biopsy for all patients; if positive, axillary node dissection

Descriptive text is not available for this image ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • Every 4 to 6 months for 5 years and then annually; mammogram 6 to 12 months post-surgery or radiation then annually
  • No evidence for routine complete blood count, LFTs, “tumor markers,” bone scan, chest x-ray, liver US, CT scans, MRI, PET
  • Annual pelvic exam on endocrine therapy; bone mineral density at baseline and follow-up when on AIs or with ovarian failure secondary to treatment

PROGNOSIS

5-year relative survival (SEER 18, all races, females): localized 99%, regional 86%, distant 31%, all stages 91%

COMPLICATIONS

  • Surgery: lymphedema, wound infections, seroma, hematoma, chronic pain, limited range of motion, poor cosmesis
  • Chemotherapy: immunosuppression, neuropathy, cardiotoxicity
  • Radiation: skin breakdown, fibrosis, chronic pain, long term increased risk of malignancy
  • Endocrine therapy: osteoporosis, endometrial CA and deep venous thrombosis

Authors

Tyler Von Steve, DO
Prarthna V. Bhardwaj, MBBS

REFERENCE

  1. American Cancer Society. About breast cancer. https://www.cancer.org/cancer/breast-cancer/about.html. Accessed November 23, 2024

Descriptive text is not available for this image CODES

ICD10

  • C50.52 Malignant neoplasm of lower-outer quadrant of breast, male
  • C50.929 Malignant neoplasm of unspecified site of unspecified male breast
  • C50.812 Malignant neoplasm of overlapping sites of left female breast
  • C50.529 Malignant neoplasm of lower-outer quadrant of unspecified male breast
  • C50.211 Malignant neoplasm of upper-inner quadrant of right female breast
  • C50.821 Malignant neoplasm of overlapping sites of right male breast
  • C50.329 Malignant neoplasm of lower-inner quadrant of unspecified male breast
  • C50.312 Malignant neoplasm of lower-inner quadrant of left female breast
  • C50.621 Malignant neoplasm of axillary tail of right male breast
  • C50.421 Malignant neoplasm of upper-outer quadrant of right male breast
  • C50.921 Malignant neoplasm of unspecified site of right male breast
  • C50.022 Malignant neoplasm of nipple and areola, left male breast
  • C50.221 Malignant neoplasm of upper-inner quadrant of right male breast
  • C50.11 Malignant neoplasm of central portion of breast, female
  • C50.02 Malignant neoplasm of nipple and areola, male
  • C50.629 Malignant neoplasm of axillary tail of unspecified male breast
  • C50.129 Malignant neoplasm of central portion of unspecified male breast
  • C50.512 Malignant neoplasm of lower-outer quadrant of left female breast
  • C50.319 Malignant neoplasm of lower-inner quadrant of unspecified female breast

SNOMED

  • 372064008 Malignant neoplasm of female breast
  • 188153009 Malignant neoplasm of lower-inner quadrant of female breast
  • 188152004 Malignant neoplasm of upper-inner quadrant of female breast
  • 188151006 Malignant neoplasm of central part of female breast
  • 188156001 Malignant neoplasm of axillary tail of female breast
  • 188147009 Malignant neoplasm of nipple and areola of female breast
  • 372095001 Malignant neoplasm of male breast
  • 188155002 Malignant neoplasm of lower-outer quadrant of female breast
  • 188154003 Malignant neoplasm of upper-outer quadrant of female breast
  • 286896005 Carcinoma breast - lower, outer quadrant
  • 286895009 Carcinoma of breast - upper, outer quadrant
  • 286894008 Carcinoma of breast - lower, inner quadrant
  • 286893002 Carcinoma of breast - upper, inner quadrant
  • 189336000 Carcinoma in situ of breast

CLINICAL PEARLS

  • U.S. women; 1 in 8 develop BC in within their lifetime, of those 1 in 3 become metastatic
  • Alcohol consumption, high BMI after menopause, and physical inactivity are modifiable risk factors of BC.
  • Normal MMG does not exclude the possibility of CA with a palpable mass.

Last Updated: 2026

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