Reproductive · PANCE / PANRE

Breast Cancer

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

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.

Try two board-style Breast Cancer questions

Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.

Question 1ReproductiveMedium
A 58-year-old woman presents with a 4-month history of a scaly, erythematous, eczematous lesion involving the right nipple and areola. She reports itching, mild burning, and intermittent serous discharge from the nipple. She has tried over-the-counter hydrocortisone with no improvement. Exam shows a unilateral, well-demarcated, crusted plaque on the nipple with areolar involvement; no palpable breast mass or axillary lymphadenopathy. Which of the following is the most likely diagnosis?
  • ANipple candidiasis
  • BSeborrheic dermatitis
  • CPaget disease of the breast
  • DAtopic dermatitis of the nipple
Reveal answer & full explanation
Correct answer: C — Paget disease of the breast
  • ANipple candidiasis
  • BSeborrheic dermatitis
  • CPaget disease of the breast✓
  • DAtopic dermatitis of the nipple

Why Paget disease of the breast is correct

  • Mammary Paget disease is an intraepidermal adenocarcinoma of the nipple, almost always associated with an underlying ductal carcinoma in situ or invasive ductal carcinoma.
  • It classically presents as a unilateral, chronic, eczematous or scaling lesion of the nipple that extends onto the areola, often with itching, burning, or bloody/serous discharge.
  • A hallmark feature is failure to respond to topical steroids.
  • Diagnosis is confirmed by full-thickness nipple skin biopsy showing Paget cells; bilateral mammography and breast MRI are then obtained to evaluate the underlying parenchyma.
  • Unilateral involvement, steroid-refractory course, and nipple-then-areola spread are the defining hallmarks.

Why the others are wrong

  • Nipple candidiasis — most often seen in lactating women, presents with intense burning during/after feeds and shiny erythema, not a chronic crusted plaque (confused-with intertrigo).
  • Seborrheic dermatitis — favors scalp, nasolabial folds, and chest; nipple involvement is uncommon and typically bilateral (anchoring on "scaly").
  • Atopic dermatitis of the nipple — typically bilateral, occurs in patients with an atopic history, and responds to topical steroids (premature closure on benign eczema).

Additional high-yield points

  • Pearl: any unilateral nipple eczema lasting more than several weeks or unresponsive to topical steroids requires biopsy to rule out Paget disease.
Question 2ReproductiveMedium
A 54-year-old woman is diagnosed with invasive ductal carcinoma of the right breast after core needle biopsy of a 2.5-cm firm, irregular mass with axillary lymphadenopathy. The tumor is high-grade and rapidly enlarging. Immunohistochemistry shows the cells are estrogen receptor-negative and progesterone receptor-negative, with strong (3+) membranous staining for HER2. Which of the following best explains this tumor's biology and its susceptibility to trastuzumab?
  • AInactivation of the TP53 tumor suppressor
  • BAmplification of the HER2/ERBB2 oncogene
  • COverexpression of the EGFR/HER1 receptor
  • DGermline BRCA1 loss-of-function mutation
Reveal answer & full explanation
Correct answer: B — Amplification of the HER2/ERBB2 oncogene
  • AInactivation of the TP53 tumor suppressor
  • BAmplification of the HER2/ERBB2 oncogene✓
  • COverexpression of the EGFR/HER1 receptor
  • DGermline BRCA1 loss-of-function mutation

Why Amplification of the HER2/ERBB2 oncogene is correct

  • HER2-positive breast cancer is driven by amplification of the ERBB2 (HER2/neu) gene, leading to overexpression of the HER2 receptor tyrosine kinase, constitutive growth-signaling, and an aggressive, high-grade, rapidly enlarging phenotype.
  • Strong (3+) membranous HER2 staining reflects that underlying gene amplification, and it is the amplified receptor that makes the tumor susceptible to trastuzumab, an anti-HER2 monoclonal antibody.
  • ASCO/CAP biomarker testing of ER, PR, and HER2 on every invasive specimen guides this targeted therapy.

Why the others are wrong

  • Overexpression of the EGFR/HER1 receptor — EGFR is overexpressed in basal-like/triple-negative disease and is the target of cetuximab-class agents; trastuzumab binds the extracellular domain of HER2, not HER1, so this would not confer susceptibility.
  • Germline BRCA1 loss-of-function mutation — classically underlies triple-negative (basal-like) cancers treated with chemotherapy and PARP inhibitors; this tumor is HER2-positive rather than triple-negative.
  • Inactivation of the TP53 tumor suppressor — is a general mechanism of carcinogenesis (Li-Fraumeni syndrome) but does not specifically explain HER2 overexpression or the response to trastuzumab seen here.
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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

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Commonly confused with

vs Fibroadenoma

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 or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.