Reproductive · PANCE / PANRE

Breast Cancer

Most common non-skin cancer in women; molecular subtypes (HR, HER2, triple-negative) drive treatment.

Also known as: breast cancer, ductal carcinoma in situ, DCIS, invasive ductal carcinoma, BRCA breast

Overview

Malignancy of breast epithelium, classified by histology (invasive ductal — most common, invasive lobular, DCIS, LCIS) and molecular subtype (hormone receptor [ER/PR] status, HER2 status, proliferation index). Triple-negative = ER−/PR−/HER2−.

Epidemiology

Most commonly diagnosed cancer worldwide; ~300,000 new US invasive cases/year, ~43,000 deaths. Lifetime risk ~13% in average-risk women; ~60-70% with BRCA1, ~45-55% with BRCA2.

🔒 Free preview limit reached

Keep reading — start your free trial

You've read your 2 free diagnosis previews. Create your free account to unlock the full Breast Cancer outline — plus all 514 diagnoses, 3,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.

Start your 7-day free trial → Sign in
Free to start · No credit card · Cancel anytime

Risk factors

  • Female sex, age
  • Family history; BRCA1/BRCA2, TP53 (Li-Fraumeni), PTEN (Cowden), CDH1, PALB2, ATM, CHEK2
  • Increased estrogen exposure: early menarche, late menopause, nulliparity, late first pregnancy, no breastfeeding, postmenopausal obesity, combined HRT
  • Personal history: previous breast cancer, atypical hyperplasia, LCIS
  • Prior chest wall radiation (especially for childhood Hodgkin)
  • Dense breast tissue
  • Alcohol intake

Pathophysiology

Stepwise genetic and epigenetic changes drive normal ductal/lobular epithelium through hyperplasia → atypia → in situ carcinoma → invasive cancer. ER-positive tumors are driven by estrogen signaling; HER2-positive by amplification of ERBB2; triple-negative often basal-like with BRCA association.

Clinical presentation

Symptoms

  • Painless palpable breast lump (most common)
  • Skin changes: dimpling, retraction, peau d'orange, erythema
  • Nipple changes: inversion, eczematous changes (Paget), bloody discharge
  • Axillary mass
  • Often asymptomatic — detected on screening mammography
  • Advanced: bone pain, dyspnea (lung/pleural mets), neurologic symptoms

Signs / physical exam

  • Firm, fixed, irregular breast mass
  • Skin tethering or dimpling, peau d'orange
  • Nipple retraction or eczematous changes
  • Axillary or supraclavicular lymphadenopathy
  • Inflammatory breast cancer: diffuse erythema, edema, warmth — often without discrete mass

Differential diagnosis

  • Fibroadenoma — Young women, mobile rubbery mass; ultrasound: well-circumscribed solid
  • Fibrocystic changes — Cyclic tenderness, lumpiness, bilateral; resolve with menses
  • Simple breast cyst — Anechoic on ultrasound; can aspirate
  • Mastitis or breast abscess — Tender, warm, erythematous; lactating or postpartum
  • Fat necrosis — History of trauma or surgery; can mimic cancer on imaging
  • Phyllodes tumor — Rapidly enlarging firm mass; spectrum benign to malignant
  • Inflammatory breast cancer (vs mastitis) — Erythema, peau d'orange, no fever, no improvement with antibiotics — biopsy mandatory
  • Paget disease of nipple — Eczematous nipple changes with underlying DCIS or invasive cancer

Diagnostic workup

Diagnostic criteria

Tissue diagnosis with histology and biomarkers required. AJCC 8th edition combines anatomic stage with biologic factors (ER, PR, HER2, grade).

Labs

  • CBC, BMP, LFTs
  • ER, PR, HER2 testing on biopsy specimen — mandatory for treatment planning
  • Ki-67 proliferation index in select cases
  • Genomic assays (Oncotype DX, MammaPrint) for select ER+ early-stage tumors
  • Genetic testing for BRCA/hereditary panel — diagnostic age <50, triple-negative, male breast cancer, bilateral, family history

Imaging

  • Diagnostic mammography ± ultrasound for symptomatic mass; ultrasound preferred for women <30
  • MRI breast — high-risk screening, evaluation of newly diagnosed cancer in select cases (lobular, dense breasts, occult primary)
  • Core needle biopsy (preferred) or surgical biopsy for tissue diagnosis
  • Staging: CT chest/abdomen/pelvis and bone scan for stage III, or symptomatic; PET-CT in advanced disease
  • Screening (USPSTF 2024 draft): biennial mammography ages 40-74 for average-risk women; supplemental MRI for high-risk (lifetime risk >20%, BRCA, prior chest radiation)

Diagnostic algorithm

flowchart TD
  A[Breast mass or<br/>abnormal mammogram] --> B[Diagnostic mammography<br/>± ultrasound]
  B --> C{BI-RADS}
  C -->|1-3| D[Routine or short-interval<br/>follow-up imaging]
  C -->|4-5| E[Core needle biopsy]
  E --> F{Pathology}
  F -->|Benign| G[Concordance review;<br/>routine surveillance]
  F -->|DCIS| H[Lumpectomy + RT or<br/>mastectomy; tamoxifen if ER+]
  F -->|Invasive cancer| I[Determine ER, PR, HER2,<br/>genomic risk]
  I --> J{Subtype}
  J -->|HR+ HER2−| K[Surgery + endocrine therapy<br/>± chemo by Oncotype]
  J -->|HER2+| L[Surgery + chemo +<br/>trastuzumab ± pertuzumab]
  J -->|Triple-negative| M[Neoadjuvant chemo +<br/>immunotherapy ± PARP]
From abnormal screening through subtype-driven breast cancer treatment.

Treatment

First-line

  • Local: lumpectomy + radiation (breast-conserving therapy) OR mastectomy; outcomes equivalent for appropriately selected patients
  • Axillary staging: sentinel lymph node biopsy (preferred); axillary lymph node dissection if positive sentinel nodes with significant burden
  • Reconstruction: implant or autologous, immediate or delayed
  • Adjuvant systemic therapy based on subtype (see by_subtype)

Hormone receptor-positive (ER+/PR+)

  • Premenopausal: tamoxifen × 5-10 years ± ovarian suppression (leuprolide, goserelin) ± aromatase inhibitor
  • Postmenopausal: aromatase inhibitor (anastrozole, letrozole, exemestane) × 5-10 years
  • Adjuvant chemotherapy based on Oncotype DX or other genomic assay for early-stage
  • CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) + endocrine therapy for advanced disease

HER2-positive

  • Trastuzumab (Herceptin) — IV anti-HER2 monoclonal antibody, 1 year
  • Pertuzumab added for higher-risk disease
  • Trastuzumab emtansine (T-DM1) for residual disease after neoadjuvant
  • Trastuzumab deruxtecan for advanced/metastatic
  • Monitor LVEF (cardiotoxicity)

Triple-negative

  • Chemotherapy is mainstay — neoadjuvant anthracycline + taxane regimens
  • Pembrolizumab added for higher-risk disease
  • Olaparib (PARP inhibitor) for BRCA-mutated advanced disease
  • Sacituzumab govitecan for metastatic

DCIS

  • Lumpectomy + radiation OR mastectomy
  • Tamoxifen × 5 years if ER+
  • Sentinel node biopsy not routine for pure DCIS treated with lumpectomy (consider for mastectomy)

Risk reduction (high-risk women)

  • Tamoxifen or raloxifene — premenopausal/postmenopausal at high risk
  • Aromatase inhibitors — postmenopausal
  • Bilateral risk-reducing mastectomy and salpingo-oophorectomy for BRCA carriers
  • Enhanced surveillance with MRI

Complications

  • Lymphedema (especially after axillary dissection + radiation)
  • Cardiotoxicity from anthracyclines, trastuzumab
  • Endometrial cancer (tamoxifen, ~2-3x risk)
  • Osteoporosis with aromatase inhibitors
  • VTE with tamoxifen
  • Cognitive effects ('chemo brain')
  • Recurrence (local, regional, distant) — bone, lung, liver, brain most common

PANCE pearls

  • Triple assessment (clinical exam + imaging + biopsy) is required for any breast mass — concordance reduces missed cancers.
  • Inflammatory breast cancer mimics mastitis but does NOT improve with antibiotics within 1-2 weeks; mandatory biopsy in any non-resolving 'mastitis.'
  • BRCA1/2 testing is indicated for breast cancer diagnosed <50 yo, triple-negative <60 yo, male breast cancer, bilateral, Ashkenazi Jewish ancestry, or strong family history.
  • Tamoxifen is contraindicated in women with prior VTE or stroke; use aromatase inhibitor or raloxifene alternatives.
  • Aromatase inhibitors work only in postmenopausal women (lack ovarian estrogen production) — confirm menopause status before use.
  • Male breast cancer is rare (~1% of breast cancer) but warrants BRCA testing in all cases.
  • Biennial mammography ages 40-74 (USPSTF 2024 draft) — high-risk women add MRI.

References

  • USPSTF 2024 — Screening for Breast Cancer: USPSTF Recommendation Statement, 2024
  • NCCN Breast 2024 — NCCN Clinical Practice Guidelines in Oncology: Breast Cancer
  • ACS 2015 — Breast Cancer Screening for Women at Average Risk: ACS Guideline Update (Oeffinger et al., JAMA 2015)
  • ASCO 2020 — Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: ASCO Clinical Practice Guideline Update

Practice Reproductive questions on FirstPassPA

Turn this outline into retention. 3,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.

Start studying free → Browse all 514 diagnoses

Related Reproductive diagnoses

Polycystic Ovary Syndrome (PCOS)EndometriosisUterine Fibroids (Leiomyoma)Abnormal Uterine BleedingPrimary AmenorrheaSecondary AmenorrheaMenopausePelvic Inflammatory Disease (PID)Bacterial VaginosisCandidal VulvovaginitisTrichomoniasisCervical Cancer and HPVEndometrial CancerOvarian Cancer

Differentials & related conditions

FibroadenomaFibrocystic Breast Changes

Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.