STEPTRACKERREPRODUCTIVE + ONCOLOGY | PATHOLOGY + GENETICS + PHARMACOLOGY | HIGH-YIELD REVIEW

Breast Carcinoma

Risk and genes, the in-situ lesions, the invasive types and their looks, and the receptor status that chooses the drug.

FOCUS ON
DCIS: calcifications, comedo necrosis, Paget of the nipple. LCIS: E-cadherin loss, incidental, risk marker. Invasive ductal (most common): hard, fixed, stellate. Invasive lobular: single-file cells, bilateral, E-cadherin lost. Inflammatory: dermal lymphatic emboli → peau d'orange. Axillary nodes = most important prognostic factor; ER/PR and HER2 guide therapy.
TYPE · TOPIC
MECHANISM · GENETICS
FEATURES
CLUE
Risk factors
Lifetime estrogen exposure + genetics
Female, age, early menarche, late menopause, nulliparity, first child after 30, postmenopausal obesity, HRT, chest radiation, atypical hyperplasia
Protective: breastfeeding, early pregnancy, exercise
Hereditary breast cancer
BRCA1 (chr 17): triple-negative, ovarian · BRCA2 (chr 13): male breast, pancreas, prostate · TP53 (Li-Fraumeni), PTEN (Cowden), CDH1, STK11
Young onset, bilateral, family clusters
Homologous-recombination DNA repair defect
Ductal carcinoma in situ
Malignant cells fill ducts, basement membrane intact
Microcalcifications on mammogram; comedo type: central necrosis + calcification
Precursor of invasive ductal carcinoma
Paget disease of the nipple
DCIS or invasive carcinoma cells spread into nipple epidermis
Eczematous, scaly, ulcerated nipple; large pale Paget cells
Almost always an underlying carcinoma
Lobular carcinoma in situ
E-cadherin (CDH1) loss; discohesive cells fill lobules
Incidental; no mass, usually no calcifications; often multifocal/bilateral
Risk marker for invasive cancer in either breast
Invasive ductal carcinoma (NST)
most common
Invasion through basement membrane with desmoplasia
Hard, fixed mass; stellate/spiculated on mammogram; skin dimpling, nipple retraction (Cooper ligaments)
Axillary nodes → lung, bone, liver, brain
Invasive lobular carcinoma
E-cadherin loss → cells don't stick
Single-file ("Indian file") cells; often bilateral, multifocal; hard to see on mammogram; ER ⁺
Unusual mets: peritoneum, GI, ovaries, meninges
Special types
Distinct morphology
Mucinous (older, pools of mucin) · tubular (well-formed tubules) · medullary features (syncytial sheets + lymphocytes, BRCA1, triple-negative)
Mucinous and tubular: good prognosis
Inflammatory carcinoma
Tumor emboli in dermal lymphatics
Red, warm, swollen breast with peau d'orange; often no discrete mass
Mimics mastitis · poor prognosis
Molecular subtypes
Luminal (ER/PR ⁺), HER2-amplified (ERBB2), basal-like/triple-negative
Triple-negative: young, Black women, BRCA1, aggressive
ER ⁺ = best prognosis
Prognosis
Spread and biology
Axillary lymph node status (single most important), size, grade, receptors
Sentinel node biopsy
Male breast cancer
BRCA2, Klinefelter, estrogen exposure
Subareolar mass, nipple discharge or retraction; usually ER ⁺ ductal
Earlier skin/chest-wall involvement

Mechanism — E-cadherin and growth pattern

E-cadherin intactCells cohesive
→
DuctalGlands, sheets, stellate mass
E-cadherin lostCDH1
→
LobularSingle-file infiltration, no mass
→
Hereditary diffuse gastric cancerSame gene

Desmoplastic stroma shortens Cooper ligaments (dimpling) and lactiferous ducts (nipple retraction).

Receptor → drug

TARGET
DRUG
NOTE
ER ⁺ (premenopausal)
Tamoxifen (SERM)
↑ endometrial cancer, DVT
ER ⁺ (postmenopausal)
Anastrozole, letrozole (aromatase inhibitors)
Bone loss
HER2 ⁺
Trastuzumab
Cardiotoxicity (reversible)
BRCA-mutant
PARP inhibitors (olaparib)
Synthetic lethality
CDK4/6
Palbociclib
With endocrine therapy

How it's tested

COMMON CONFUSIONDCIS presents as calcifications and is a direct precursor. LCIS is usually found by chance and marks risk in both breasts rather than at that exact spot.
THE TRAP"Mastitis" in a non-lactating woman that doesn't respond to antibiotics is inflammatory carcinoma until biopsy says otherwise.
YOUR APPROACHPresentation (calcs, mass, nipple, red breast) → in situ vs invasive → ductal vs lobular (E-cadherin) → receptors → nodes → targeted therapy.

If you see… think…

Clustered microcalcifications, ducts with central necrosis → comedo DCIS
Scaly ulcerated nipple with large pale intraepidermal cells → Paget disease — find the cancer
Incidental lobular lesion with E-cadherin loss → LCIS
Hard fixed mass with skin dimpling → invasive ductal carcinoma
Single-file tumor cells, E-cadherin negative → invasive lobular carcinoma
Red swollen breast with orange-peel skin, no mass → inflammatory carcinoma
Young woman, triple-negative tumor with lymphocytes → BRCA1-associated carcinoma
Male breast cancer + family pancreatic cancer → BRCA2
HER2-amplified tumor → trastuzumab (watch cardiac function)
Single most important prognostic factor → axillary lymph node involvement