Eduovisual
Female Reproductive & Breast
Breast cancer: staging and treatment overview
— Most common non-skin cancer in US women; lifetime risk ~12–13% (1 in 8)
— Median age at diagnosis ~62; second leading cause of cancer death in women after lung
— ~85% sporadic, ~15% hereditary (BRCA1/2, PALB2, TP53, CHEK2, ATM, CDH1)
— Screening-detected mammographic abnormality (mass, asymmetry, microcalcifications, architectural distortion) — by far the most common stem opener
— Palpable breast mass: hard, fixed, irregular, painless; especially in women >40
— Unilateral bloody or serous nipple discharge, skin dimpling, peau d'orange, nipple retraction
— Axillary lymphadenopathy without clear infectious source
— Paget disease: eczematous, scaly, ulcerated nipple unresponsive to topical steroids
— Inflammatory breast cancer: rapid-onset erythema, warmth, edema mimicking mastitis but not improving with antibiotics in 1–2 weeks
— Biennial mammography ages 40–74 (Grade B); individualize >75
— ACS option: annual 40–44, annual 45–54, then annual or biennial ≥55
— High-risk (lifetime risk ≥20% by Tyrer-Cuzick/BRCAPRO, BRCA carriers, chest XRT age 10–30): add annual breast MRI alternating q6mo with mammography starting age 25–30
— Non-modifiable: age, female sex, family history, early menarche (<12), late menopause (>55), nulliparity, dense breasts, prior atypical hyperplasia/LCIS, prior chest radiation
— Modifiable: postmenopausal obesity, alcohol (>1 drink/day), combined HRT >5 yr, physical inactivity
Board pearl: A woman with persistent unilateral "mastitis" not resolving after a course of antibiotics needs skin punch biopsy and diagnostic imaging to rule out inflammatory breast cancer — do not keep cycling antibiotics. Inflammatory breast cancer is clinically defined (T4d) regardless of underlying histology and is treated as locally advanced disease from the outset.
— Asymptomatic 55-year-old, screening mammogram shows clustered pleomorphic microcalcifications → DCIS until proven otherwise
— 48-year-old finds a firm, immobile lump on self-exam, painless → invasive ductal carcinoma (IDC, ~75% of invasive cases)
— 65-year-old with vague thickening, no discrete mass, mammographically subtle → invasive lobular carcinoma (ILC); often bilateral, multifocal, harder to image
— Postmenopausal woman with unilateral bloody nipple discharge from a single duct → consider intraductal papilloma vs. DCIS; needs ductography or surgical duct excision
— Young woman, rapidly enlarging painless mass, mobile, well-circumscribed → likely phyllodes vs. fibroadenoma; excisional biopsy because core may miss phyllodes
— Pregnant or postpartum woman with palpable mass → do not dismiss as lactational change; ultrasound first, then biopsy if suspicious
— Duration, growth rate, skin or nipple changes, relation to menses
— Reproductive: age at menarche/menopause, parity, age at first live birth, breastfeeding duration, HRT/OCP use
— Family history: first- and second-degree relatives with breast, ovarian, pancreatic, prostate cancer; Ashkenazi Jewish ancestry (BRCA founder mutations)
— Personal history of prior biopsy (ADH, ALH, LCIS), chest radiation (mantle field for Hodgkin), prior contralateral breast cancer
— Symptoms of metastasis: bone pain, weight loss, dyspnea, headache, abdominal pain, jaundice
— Breast cancer ≤45, triple-negative ≤60, bilateral disease, male breast cancer, ≥2 primaries, Ashkenazi ancestry, ovarian/pancreatic/metastatic prostate cancer in family, known familial mutation
Key distinction: Cyclic, bilateral, diffuse breast pain with lumpiness that varies with menses is fibrocystic change — reassurance and reimaging if persistent. A fixed, firm, painless, unilateral mass in a woman >40 demands triple assessment (clinical exam + imaging + tissue) regardless of how "benign" it feels. Pain does not rule out cancer (~10% of cancers present with pain).
— Asymmetry, skin dimpling/tethering (Cooper ligament involvement), nipple inversion (new, unilateral), erythema, edema, peau d'orange (dermal lymphatic invasion → T4b/inflammatory)
— Paget disease: unilateral eczematous, scaly, crusted, or ulcerated nipple-areolar complex; underlying DCIS or invasive cancer in >95%
— Visible mass, ulceration, satellite skin nodules (T4b)
— Characterize: location (clock face + cm from nipple), size, consistency (hard vs. rubbery), borders (irregular vs. smooth), mobility (fixed to skin/chest wall = T4a)
— Examine entire breast, axillary tail of Spence, and nipple — express only if patient reports discharge
— Nipple discharge red flags: unilateral, single duct, spontaneous, bloody or serous, associated mass
— Axillary (levels I–III), supraclavicular, infraclavicular, internal mammary (not palpable)
— Ipsilateral supraclavicular node = N3c → stage IIIC; contralateral axillary or supraclavicular node = M1 (stage IV)
— Matted or fixed axillary nodes = N2
— Spine/pelvis tenderness (bone — most common metastatic site), hepatomegaly, ascites, pleural effusion, neurologic deficits
— T1 ≤2 cm, T2 >2–5 cm, T3 >5 cm, T4 skin/chest wall/inflammatory
— Always document cT, cN, and clinical stage before biopsy results return
Step 3 management: On a palpable breast mass exam, the correct next-step phrasing is "diagnostic mammogram and targeted ultrasound," then core needle biopsy of any BI-RADS 4–5 finding — not excisional biopsy first, not FNA (insufficient for receptor testing), and not "repeat exam in 3 months" in a woman >30 with a dominant mass.
— First imaging in women ≥30 with palpable or suspicious finding
— Reports use BI-RADS:
— 0 incomplete (need more imaging), 1 negative, 2 benign, 3 probably benign (<2% malignancy → 6-mo follow-up), 4 suspicious (2–95%) → biopsy, 5 highly suggestive (>95%) → biopsy, 6 known malignancy
— Suspicious features: spiculated mass, pleomorphic clustered microcalcifications, architectural distortion, new asymmetry
— First-line imaging if <30 yr, pregnant, or lactating
— Adjunct to mammography in dense breasts and to characterize masses (cyst vs. solid)
— Also images axilla: cortical thickening >3 mm or loss of fatty hilum → biopsy node
— Indications: known BRCA/high-risk screening, occult primary with axillary metastasis, evaluation of extent in newly diagnosed ILC, response to neoadjuvant therapy, problem-solving when mammo/US discordant
— Not a substitute for tissue diagnosis; high sensitivity, moderate specificity
— Core needle biopsy (image-guided) is the standard — provides histology, grade, and ER/PR/HER2 status
— Stereotactic core for calcifications, US-guided core for masses, MRI-guided for MRI-only lesions
— FNA is inadequate (cannot distinguish invasive from in situ, no receptor testing on small samples)
— Excisional biopsy reserved for discordant results, papillary lesions, or phyllodes suspicion
— CBC, CMP, LFTs, alkaline phosphatase
— Tumor markers (CA 15-3, CEA) not recommended for screening or initial staging — used selectively to follow metastatic disease
CCS pearl: Order "diagnostic mammogram bilateral + targeted breast ultrasound" together for a palpable mass; advance the simulated clock; then order "ultrasound-guided core needle biopsy of right breast mass" with ER/PR/HER2 testing. Avoid ordering MRI before tissue diagnosis unless it's a high-risk screening scenario.
— Invasive ductal carcinoma (NST) ~75% — most common
— Invasive lobular carcinoma ~10–15% — loss of E-cadherin, single-file infiltration, often ER+/HER2−, multifocal/bilateral
— Special types: tubular, mucinous, medullary (favorable); metaplastic, inflammatory (unfavorable)
— In situ: DCIS (precursor, treated as cancer); LCIS is a risk marker, not a precursor — does not require excision but warrants risk reduction
— ER and PR (positive if ≥1% nuclei stain) → endocrine therapy eligible
— HER2 by IHC (0, 1+, 2+, 3+); 2+ reflexes to FISH; 3+ or FISH-amplified = HER2-positive → anti-HER2 therapy
— HER2-low (IHC 1+ or 2+/FISH−) now actionable in metastatic disease with trastuzumab deruxtecan
— Triple-negative (ER−/PR−/HER2−): aggressive, often BRCA-associated, chemo-responsive
— Oncotype DX 21-gene Recurrence Score: ER+/HER2−, node-negative (and select 1–3 node-positive postmenopausal) — guides chemo addition to endocrine therapy
— MammaPrint, Prosigna, EndoPredict as alternatives
— Stage I–II asymptomatic: routine systemic imaging not indicated (low yield, false positives)
— Stage III, inflammatory, or symptomatic: CT chest/abdomen/pelvis + bone scan (or FDG-PET/CT)
— Brain imaging only if neurologic symptoms (or HER2+/TNBC with high suspicion)
— Combines anatomic TNM with biologic factors (grade, ER/PR/HER2, genomic score) → prognostic stage often differs from anatomic
Board pearl: A triple-negative breast cancer in a 38-year-old → refer for germline BRCA1/2 testing regardless of family history; result alters surgical decisions (contralateral prophylactic mastectomy), systemic therapy (PARP inhibitor candidacy with olaparib), and family screening.
— Stage 0 (DCIS): breast-conserving surgery (BCS) + whole-breast radiation OR mastectomy; endocrine therapy if ER+ to reduce ipsilateral recurrence and contralateral cancer
— Stage I–II (early invasive): surgery first → adjuvant systemic ± radiation, unless HER2+ ≥T2 or TNBC ≥T2 (favor neoadjuvant)
— Stage III (locally advanced, including inflammatory): neoadjuvant systemic therapy first, then surgery (mastectomy or BCS if response), then radiation
— Stage IV (metastatic): systemic therapy is mainstay; surgery/radiation for palliation; goal is disease control and quality of life
— ER+/HER2−: endocrine therapy backbone ± CDK4/6 inhibitor (abemaciclib adjuvant for high-risk node+); chemo only if high genomic risk or high clinical risk
— HER2+: anti-HER2 therapy (trastuzumab ± pertuzumab) + chemo; neoadjuvant TCHP for ≥T2 or node+
— TNBC: chemotherapy-based; pembrolizumab added neoadjuvantly/adjuvantly for ≥T2 or node+ (KEYNOTE-522)
— Downstages tumors to allow BCS, eradicates micrometastatic disease early, provides in vivo chemo-sensitivity data, identifies residual disease for escalation (T-DM1 for HER2+, capecitabine for TNBC, olaparib for BRCA+)
— Surgical oncology, medical oncology, radiation oncology, pathology, radiology, genetics, plastic surgery, social work — Step 3 favors tumor board referral for stage II+ disease
Step 3 management: When the stem gives you a newly diagnosed T2N1 HER2+ or triple-negative tumor, the correct next step is neoadjuvant systemic therapy, not upfront mastectomy. Conversely, a 1.5 cm ER+/HER2−/node-negative tumor in a 65-year-old → lumpectomy + sentinel lymph node biopsy first, then Oncotype DX to decide on chemotherapy.
— Premenopausal: tamoxifen (SERM) ± ovarian suppression (GnRH agonist); aromatase inhibitor (AI) only with concurrent ovarian suppression
— Postmenopausal: AI (anastrozole, letrozole, exemestane) preferred; tamoxifen if AI intolerant
— Extended therapy to 10 years for high-risk (node+, large tumor) reduces late recurrence
— Adverse effects: tamoxifen → VTE, endometrial cancer, hot flashes, cataracts; AI → arthralgia, osteoporosis (need DEXA, calcium, vitamin D), hyperlipidemia
— Adjuvant abemaciclib × 2 years for high-risk node-positive (monarchE)
— Metastatic: palbociclib, ribociclib, abemaciclib + AI (1st line) or fulvestrant (2nd line); ribociclib has overall survival benefit
— Monitor CBC (neutropenia), LFTs, QTc (ribociclib), diarrhea (abemaciclib)
— Adjuvant trastuzumab × 1 year (+ pertuzumab if node+); TCHP neoadjuvant for stage II–III
— Residual disease after neoadjuvant → T-DM1 × 14 cycles (KATHERINE)
— Metastatic: 1st line THP; 2nd line trastuzumab deruxtecan (T-DXd); monitor for cardiotoxicity (LVEF q3mo) and pneumonitis (T-DXd)
— AC-T (doxorubicin/cyclophosphamide → paclitaxel); TC (docetaxel/cyclophosphamide) for lower-risk; TCHP for HER2+
— TNBC neoadjuvant: carboplatin + taxane → AC, + pembrolizumab (KEYNOTE-522)
— Olaparib × 1 year adjuvantly for germline BRCA1/2 + high-risk HER2− disease (OlympiA)
Board pearl: A premenopausal woman started on an AI without ovarian suppression will have paradoxically elevated estrogen from unopposed pituitary feedback — AIs require either confirmed menopause or concurrent GnRH agonist (goserelin, leuprolide) or oophorectomy.
— Breast-conserving surgery (lumpectomy) + whole-breast radiation = equivalent survival to mastectomy for eligible patients (NSABP B-06)
— Mastectomy indicated for: multicentric disease, diffuse malignant calcifications, inability to achieve negative margins, prior chest radiation, large tumor:breast ratio, patient preference, BRCA carriers
— Margins: "no ink on tumor" for invasive cancer; 2 mm for DCIS
— Contralateral prophylactic mastectomy: reasonable only for BRCA/high-risk germline carriers — no survival benefit otherwise
— Sentinel lymph node biopsy (SLNB) is standard for clinically node-negative disease
— Z0011 trial: T1–T2, cN0, 1–2 positive sentinels, BCS + whole-breast XRT, planned adjuvant therapy → no completion ALND needed
— Axillary lymph node dissection (ALND) for: ≥3 positive sentinels, clinically positive nodes pre-neoadjuvant that remain positive, inflammatory cancer, mastectomy with positive SLN (case-by-case)
— Post-neoadjuvant cN1→cN0: targeted axillary dissection (dual tracer + clip retrieval)
— Whole-breast XRT after every lumpectomy (hypofractionated 15–16 fractions standard); omission considered in women ≥70, T1, ER+, node-negative taking endocrine therapy (CALGB 9343)
— Post-mastectomy radiation (PMRT): tumor >5 cm, positive margins, ≥4 positive nodes, inflammatory cancer, T4 disease; consider for 1–3 nodes
— Regional nodal irradiation (supraclav, internal mammary, axilla) for node-positive disease
— Immediate vs. delayed; implant-based or autologous (DIEP, TRAM, latissimus); coordinate with radiation plans (radiation worsens implant outcomes)
Key distinction: A 72-year-old with a 1.2 cm ER+/HER2−, cN0 tumor on tamoxifen can omit radiation after lumpectomy (PRIME II, CALGB 9343) — local recurrence rises modestly but survival is unchanged. Don't reflexively radiate every elderly lumpectomy patient.
— Assess with geriatric assessment (G8, CARG score) — chronologic age alone should not dictate therapy
— Consider de-escalation: omit radiation in low-risk ER+ tumors, oral chemo (capecitabine) over IV anthracyclines if frail
— CALGB 49907: standard AC or CMF superior to capecitabine monotherapy in fit ≥65 — don't undertreat the fit elderly
— Monitor anthracycline cardiotoxicity carefully; LVEF threshold and HFpEF risk higher
— Bone health: AIs + age → high fracture risk; DEXA at baseline and q2y, calcium 1200 mg/d, vitamin D 800–1000 IU/d, consider denosumab or zoledronic acid
— Capecitabine: reduce dose if CrCl 30–50; contraindicated CrCl <30
— Cisplatin/carboplatin: dose by Calvert formula (carboplatin); avoid cisplatin if CrCl <60
— Methotrexate (CMF regimen): avoid if CrCl <60
— Tamoxifen and AIs do not require renal dose adjustment
— Gadolinium MRI: avoid linear agents if eGFR <30 (NSF risk)
— Anthracyclines, taxanes, vinorelbine: reduce dose for elevated bilirubin/transaminases
— Tamoxifen: caution — can cause hepatic steatosis; AIs metabolized hepatically
— CDK4/6 inhibitors: dose reduce in Child-Pugh B/C
— Trastuzumab: no hepatic adjustment but monitor LVEF
— Baseline echo before anthracyclines and trastuzumab; LVEF must be ≥50–55%
— Hold trastuzumab if LVEF drops ≥10 points to <50%
— Consider non-anthracycline regimens (TC, TCHP) in cardiac risk
Step 3 management: A 78-year-old with stage I ER+/HER2− invasive ductal carcinoma, lumpectomy completed, ECOG 1, no significant comorbidity — start anastrozole + calcium/vit D + baseline DEXA, discuss radiation omission per CALGB 9343, and do not order Oncotype if you've already decided against chemo regardless of result.
— Diagnosed during pregnancy or within 1 year postpartum; often delayed diagnosis from attribution to lactational changes
— Ultrasound first; mammogram with abdominal shielding is safe; MRI with gadolinium avoided
— Core biopsy safe in all trimesters
— Surgery safe in any trimester (modified radical mastectomy historically preferred; BCS feasible with delayed radiation)
— Chemotherapy: anthracycline + cyclophosphamide ± taxane safe in 2nd and 3rd trimesters; avoid in 1st trimester (teratogenic)
— Contraindicated in pregnancy: tamoxifen, AIs, trastuzumab (oligohydramnios, renal agenesis), pertuzumab, radiation
— Deliver at term (≥37 wk); avoid chemo within 3 weeks of delivery (neonatal myelosuppression)
— Therapeutic abortion does not improve outcomes — counsel that pregnancy can continue
— Often more aggressive biology (higher TNBC, HER2+ rates), worse prognosis stage-for-stage
— Fertility preservation referral before chemo: oocyte/embryo cryopreservation; GnRH agonist (goserelin) during chemo reduces premature ovarian insufficiency
— Genetic testing strongly recommended
— Contraception during therapy (non-hormonal: copper IUD)
— Pregnancy after treatment: safe after 2 years (POSITIVE trial — pause endocrine therapy after ≥18 months for pregnancy attempt)
— Almost always ER+; strong association with BRCA2 (test all men with breast cancer)
— Treatment: mastectomy + SLNB, tamoxifen standard (AIs less effective without ovarian suppression analogue — males require GnRH if AI used)
— Screening: no population screening; BRCA2 carriers — annual clinical breast exam from age 35
Board pearl: A pregnant woman with newly diagnosed invasive breast cancer in the 2nd trimester gets AC chemotherapy now, mastectomy or lumpectomy as needed, and defers tamoxifen, trastuzumab, and radiation until after delivery — pregnancy termination is not required and does not improve survival.
— Bone metastases (most common — ~70% of metastatic): pain, pathologic fracture, hypercalcemia, spinal cord compression → MRI whole spine emergently, dexamethasone, neurosurgery/radiation
— Brain metastases: more common in HER2+ and TNBC; MRI brain for neurologic symptoms; SRS for limited, WBRT for diffuse
— Malignant pleural effusion: thoracentesis, pleurodesis or indwelling catheter
— Lymphangitic carcinomatosis, liver failure, hypercalcemia of malignancy
— Chemotherapy: febrile neutropenia (G-CSF prophylaxis for >20% risk regimens), nausea, alopecia, mucositis, peripheral neuropathy (taxanes), cardiotoxicity (anthracyclines — cumulative dose limit doxorubicin 450–500 mg/m²)
— Trastuzumab: reversible LV dysfunction (vs. anthracycline irreversible); monitor LVEF q3 mo
— Tamoxifen: VTE (2–3×), endometrial cancer (2–7×), cataracts, hot flashes; investigate any postmenopausal bleeding with TVUS + endometrial biopsy
— AIs: osteoporosis/fractures, arthralgias (often limit adherence), hyperlipidemia, vaginal dryness
— CDK4/6 inhibitors: neutropenia, diarrhea (abemaciclib), pneumonitis, hepatotoxicity, QT prolongation (ribociclib)
— Immunotherapy (pembrolizumab): thyroiditis, pneumonitis, colitis, hepatitis, hypophysitis — check TSH q cycle
— PARP inhibitors: myelosuppression, MDS/AML (rare), pneumonitis
— Lymphedema (post-ALND ~20%, post-SLNB ~5%): early PT referral, compression sleeves, avoid BP/IV in affected arm
— Seroma, infection, chronic post-mastectomy pain, frozen shoulder
— Radiation: skin desquamation, pneumonitis, cardiac (left-sided breast — modern techniques minimize), secondary angiosarcoma (rare, late)
Key distinction: Trastuzumab-induced cardiotoxicity is typically reversible with drug hold and standard HF therapy; anthracycline cardiotoxicity is dose-dependent and largely irreversible — this distinction drives sequencing and monitoring decisions.
— Febrile neutropenia (ANC <500 + temp ≥38.3 or ≥38.0 sustained 1 h): blood cultures × 2, urine, CXR, empiric cefepime or piperacillin-tazobactam within 1 hour; add vancomycin if line/skin source, hemodynamically unstable, or MRSA risk; ICU if septic shock
— Spinal cord compression: new back pain + neuro deficit → dexamethasone 10 mg IV stat, MRI whole spine, neurosurgery + rad onc consult emergently; outcomes hinge on ambulation status at treatment
— Hypercalcemia of malignancy: Ca >12 symptomatic → IV normal saline 200–300 mL/h, zoledronic acid 4 mg IV (or denosumab if renal failure), calcitonin for rapid effect; loop diuretics only after euvolemia
— SVC syndrome: facial/upper extremity swelling, plethora → CT chest, elevate HOB, steroids, radiation or endovascular stent; tissue diagnosis before treatment unless airway compromise
— Brain mets with mass effect/herniation: dexamethasone 10 mg IV, mannitol if herniation, neurosurgery
— Tumor lysis syndrome: rare in breast cancer, but high-volume liver/bone disease starting chemo — hydration, allopurinol/rasburicase, monitor electrolytes
— Uncontrolled pain, intractable vomiting, dehydration, severe diarrhea (CDK4/6, capecitabine), grade 3–4 immune-related adverse events, suspected sepsis, new altered mental status, hyponatremia
— Medical oncology (always), surgical oncology, radiation oncology, plastic surgery, genetics, fertility, palliative care (early, parallel with active treatment per ASCO), psycho-oncology, social work, lymphedema PT
CCS pearl: For a patient on AC chemotherapy presenting with T 38.5°C and ANC 300, the order set is: blood cultures × 2 (peripheral + port), UA/Cx, CXR, lactate, CBC, CMP, then immediately empiric cefepime IV — do not wait for cultures to return. Advance the clock; reassess hemodynamics; add vancomycin if no improvement at 48–72 h or unstable.
— Fibroadenoma: young women (15–35), mobile, rubbery, well-circumscribed, "breast mouse"; US shows oval, parallel orientation; observe or excise if growing/symptomatic
— Phyllodes tumor: rapidly growing, can be benign/borderline/malignant; wide local excision (≥1 cm margin); no SLNB (spread hematogenous)
— Intraductal papilloma: unilateral bloody nipple discharge, subareolar; excise — may harbor atypia or DCIS
— Lipoma, hamartoma, granular cell tumor
— Simple cyst: anechoic on US, BI-RADS 2 — aspirate only if symptomatic; bloody aspirate or residual mass → biopsy
— Complex cystic mass: biopsy
— Lactational mastitis/abscess: tender, erythematous, fluctuant in breastfeeding woman → dicloxacillin or cephalexin; drainage if abscess; continue breastfeeding
— Periductal mastitis (smokers): subareolar abscess, may fistulize
— Fat necrosis: post-trauma or post-surgical; oil cyst with rim calcifications — often mimics cancer; may need biopsy
— Atypical ductal hyperplasia (ADH): found on core biopsy → excisional biopsy (15–30% upgrade to DCIS/invasive)
— Atypical lobular hyperplasia (ALH) / LCIS: risk markers (RR 4–10×); endocrine risk reduction (tamoxifen, raloxifene, AI); pleomorphic LCIS → excise
— Radial scar/complex sclerosing lesion: excise to rule out occult malignancy
— Flat epithelial atypia
— Mastitis: lactating, responds to antibiotics in 48–72 h
— IBC: no response in 1–2 weeks, often non-lactating, peau d'orange, diffuse — skin punch biopsy + core biopsy of underlying tissue
Board pearl: Any core biopsy returning ADH, papilloma with atypia, radial scar, or flat epithelial atypia mandates surgical excisional biopsy, because rates of upgrade to DCIS or invasive cancer range 10–30%. Don't accept the core biopsy as final.
— Occult breast primary (CUP, axillary presentation): mammogram negative, MRI breast finds primary in ~70%
— Lymphoma (firm, rubbery, multiple stations, B symptoms) — excisional node biopsy
— Melanoma, lung, ovarian, thyroid metastasis
— Cat-scratch disease, TB, sarcoidosis, HIV
— Cellulitis, abscess (responds to antibiotics)
— Erysipelas
— Radiation dermatitis (history-dependent)
— Mondor disease (superficial thrombophlebitis — palpable cord)
— Cutaneous T-cell lymphoma, mycosis fungoides
— Paget disease vs. eczema/contact dermatitis: eczema typically bilateral, spares nipple-areolar complex initially; Paget is unilateral, starts at nipple, fails topical steroids → punch biopsy of nipple
— Nipple adenoma, nipple duct ectasia
— Metastatic recurrence (bone scan, MRI)
— Aromatase inhibitor arthralgia (symmetric, joints, no focal lesion)
— Osteoporotic fracture
— Bisphosphonate-related osteonecrosis of jaw (dental disease in patient on zoledronic acid/denosumab — dental clearance before therapy)
— Metastasis vs. primary lung cancer (smoker), granulomatous disease, infection — biopsy if changes management
— Metastasis vs. hepatic hemangioma, FNH, adenoma — MRI characterization, biopsy if uncertain
Key distinction: Paget disease of the nipple = unilateral, eczematoid, fails topical steroids, almost always has underlying DCIS or invasive cancer → mammography + breast MRI + punch biopsy of nipple. Bilateral itchy nipples in an atopic patient = eczema → topical steroid trial first.
— Premenopausal: tamoxifen 5–10 years ± ovarian suppression for high risk (SOFT/TEXT)
— Postmenopausal: AI 5 years, extend to 7–10 if high risk and tolerating
— Adherence is the #1 modifiable survival factor — address hot flashes (venlafaxine, gabapentin; avoid paroxetine/fluoxetine with tamoxifen — CYP2D6 inhibition reduces active metabolite), vaginal dryness (non-hormonal lubricants; vaginal estrogen controversial but generally safe), joint pain (exercise, duloxetine, switch AI)
— Baseline DEXA, repeat q2y; calcium 1200 mg/d + vitamin D 800–2000 IU/d; weight-bearing exercise
— Bisphosphonate or denosumab for T-score ≤−2.0 or osteoporosis; adjuvant zoledronic acid reduces recurrence in postmenopausal women (EBCTCG)
— Weight management (BMI 20–25): obesity worsens recurrence in ER+ disease
— Exercise ≥150 min/week moderate aerobic + 2× resistance training — reduces all-cause and breast-cancer mortality
— Alcohol ≤1 drink/day (ideally less)
— Smoking cessation
— Mediterranean-style diet
— Influenza annually, pneumococcal per age, recombinant zoster ≥50, COVID boosters; avoid live vaccines during immunosuppressive therapy
— Annual mammography of remaining breast tissue (or both breasts if BCS) — first mammogram 6–12 months after radiation completion
— MRI surveillance for BRCA carriers, dense breasts, age <50 at diagnosis with extremely dense tissue
— No role for routine CT, bone scan, tumor markers, or PET in asymptomatic survivors (ASCO Choosing Wisely)
Step 3 management: A 52-year-old, 2 years post-lumpectomy/XRT for stage I ER+ breast cancer on anastrozole, develops postmenopausal vaginal bleeding. Stop and consider: she's on an AI not tamoxifen — endometrial cancer risk is not elevated by AIs (lower than tamoxifen), but PMB still warrants TVUS + endometrial biopsy. Don't blame the AI.
— History + physical: every 3–6 months × 3 years, then every 6–12 months × 2 years, then annually
— Mammography: annual (both breasts if BCS); first at 6–12 months post-radiation
— Gynecologic exam: annual; on tamoxifen — report any abnormal bleeding immediately (workup PMB with TVUS + endometrial biopsy)
— DEXA: baseline, then q2y on AI or premenopausal on ovarian suppression
— Echo/MUGA: baseline before anthracycline/trastuzumab, q3 mo during trastuzumab, then per symptoms
— Lipid panel: annually on AI
— No routine: CBC, LFTs, tumor markers, CT, bone scan, PET in asymptomatic patients
— New bone pain: x-ray then bone scan or MRI
— Persistent cough/dyspnea: CT chest
— Neurologic symptoms: MRI brain
— RUQ pain, abnormal LFTs: imaging
— Weight loss: directed workup
— Lymphedema prevention: PT referral, education, compression; early intervention if circumference ↑ ≥2 cm; modern data suggest BP and blood draws in the at-risk arm are lower risk than historically taught, but most still avoid when possible
— Shoulder ROM exercises post-mastectomy/ALND
— Sexual health: vaginal moisturizers, counseling; consider pelvic floor PT
— Cognitive concerns ("chemo brain"): exercise, cognitive training, sleep hygiene
— Fatigue: structured exercise is the best intervention
— Mental health: screen for depression/anxiety at every visit (PHQ-9, GAD-7); ~25% of survivors have clinically significant distress
— Survivorship care plan at completion of active treatment summarizing treatments, expected late effects, surveillance schedule, lifestyle recommendations — handed off to PCP
CCS pearl: At a survivorship visit, the value-added orders are focused H&P, mammogram (if due), DEXA (if due), PHQ-9, counseling on exercise/alcohol/weight, and confirmation of endocrine therapy adherence — not a "full restaging" CT/bone scan/tumor marker panel, which is a Choosing Wisely violation in asymptomatic survivors.
— Must cover: nature of cancer, treatment options including observation/no treatment for select DCIS or frail elderly, expected benefits, risks (including infertility from chemo, premature menopause, secondary malignancy from radiation/alkylators), alternatives, and uncertainty
— Fertility preservation discussion is a quality metric — document offer in every woman <45 before gonadotoxic therapy (ASCO mandate)
— Genetic testing requires pre-test counseling about implications for family members, insurance (GINA protects health insurance but NOT life/disability insurance), and psychological impact
— Lumpectomy vs. mastectomy when both oncologically equivalent — patient values, body image, radiation tolerance
— Contralateral prophylactic mastectomy in non-BRCA patients — no survival benefit; counsel against unless strong patient preference after informed discussion
— Chemotherapy when Oncotype is intermediate — quantify absolute benefit (often <3–5%)
— Hand-off from oncology to PCP at ~5 years requires survivorship care plan; without it, surveillance gaps and missed late effects are common (anthracycline cardiomyopathy 10+ years out, secondary malignancies)
— Medication reconciliation at every transition — endocrine therapy adherence drops to ~50% by year 5
— Communicate radiation field to PCP — left-chest XRT survivors need cardiovascular risk vigilance
— Disclose medical errors (wrong-site surgery is a never-event; bilateral surgical site marking with patient awake is standard)
— Report cancer diagnoses to state cancer registry (legally required in all US states)
— Report suspected child abuse if identified during family discussions (mandated reporter status)
— Use professional medical interpreters (not family members) — failure is a documented safety event
— Address financial toxicity: ~30% of breast cancer patients face significant financial strain; refer to social work, patient assistance programs
— Assess capacity for each major decision; document
— Encourage advance care planning, especially in metastatic disease — early palliative care improves outcomes and survival
Step 3 management: A 32-year-old newly diagnosed with stage II HER2+ breast cancer is being scheduled for AC-THP. The correct next step before chemo starts is referral for fertility preservation (oocyte/embryo cryopreservation, ~2-week process) — delaying chemo briefly is acceptable and is the standard of care; failure to offer is a documented quality lapse.
— BRCA1: triple-negative, basal-like, ovarian cancer, younger onset; lifetime breast risk ~60–70%, ovarian ~40%
— BRCA2: ER+, male breast cancer, pancreatic, prostate; breast risk ~50–60%
— Li-Fraumeni (TP53): breast cancer <30, sarcoma, brain, adrenal, leukemia — avoid radiation when possible
— Cowden (PTEN): breast, thyroid (follicular), endometrial, macrocephaly, hamartomas
— CDH1: lobular breast cancer + diffuse gastric cancer (prophylactic gastrectomy)
— PALB2: breast risk approaches BRCA2
— ER+ → endocrine therapy
— HER2+ → trastuzumab/pertuzumab/T-DM1/T-DXd
— TNBC → chemo + pembrolizumab (PD-L1+); BRCA+ → olaparib; trop-2 ADC sacituzumab govitecan in metastatic
— ER+/HER2−/high-risk node+ → adjuvant abemaciclib
— NSABP B-06: BCS + XRT = mastectomy
— Z0011: SLN positive (1–2 nodes) + BCS → no ALND
— MA.17R/ATLAS/aTTom: extended endocrine therapy benefits
— CALGB 9343/PRIME II: XRT omission in elderly low-risk
— KEYNOTE-522: pembrolizumab in TNBC
— OlympiA: olaparib in BRCA+ HER2− adjuvant
— monarchE: adjuvant abemaciclib
— DESTINY-Breast04: T-DXd for HER2-low metastatic
— POSITIVE: safe to pause endocrine therapy for pregnancy
— ILC favors peritoneum, GI tract, ovary (atypical sites — beware bowel obstruction or "primary ovarian" that's actually metastatic ILC)
— Tamoxifen + paroxetine/fluoxetine = reduced efficacy (CYP2D6) — use venlafaxine for hot flashes
— Trastuzumab + anthracycline = additive cardiotoxicity — sequence, don't combine
— AIs + bisphosphonates = improved DFS in postmenopausal
Board pearl: A woman with lobular breast cancer presenting later with bowel obstruction, peritoneal carcinomatosis, or an "ovarian mass" — biopsy and stain for GCDFP-15, mammaglobin, GATA3, ER to confirm metastatic lobular breast rather than primary GI/GYN malignancy. This changes treatment entirely.
— Asymptomatic 55-yr-old with new clustered pleomorphic microcalcifications on mammogram → stereotactic core needle biopsy (not 6-month follow-up, not MRI, not excision)
— 28-yr-old with mobile, rubbery 2-cm mass → ultrasound first → likely fibroadenoma → observation or excision based on size/symptoms; biopsy if BI-RADS 4+
— 52-yr-old, non-lactating, with 3 weeks of breast erythema/edema unresponsive to two antibiotic courses → skin punch biopsy + diagnostic mammogram + core biopsy for inflammatory breast cancer
— Survivor on year 3 of tamoxifen with vaginal bleeding → TVUS + endometrial biopsy, do not stop tamoxifen empirically
— 45-yr-old, 4-cm tumor, palpable axillary node, HER2+ → neoadjuvant TCHP, then surgery, then complete trastuzumab/pertuzumab; T-DM1 if residual disease
— 74-yr-old, 1.2 cm ER+/HER2−/node-negative IDC after lumpectomy → anastrozole; radiation may be omitted per CALGB 9343
— 36-yr-old with 3-cm TNBC → germline BRCA testing + neoadjuvant pembrolizumab/carbo/taxane→AC; consider olaparib adjuvantly if BRCA+ with residual disease
— New back pain + lower extremity weakness in patient with prior breast cancer → MRI whole spine + dexamethasone 10 mg IV + emergent radiation/neurosurgery consult
— Day 10 post-AC, T 38.5, ANC 400 → cultures + cefepime within 1 hour, admit
— 30-yr-old, 22 weeks pregnant, biopsy-proven invasive cancer → AC chemotherapy now, defer endocrine/trastuzumab/radiation until postpartum, do not recommend termination
Key distinction: Stem buzzwords — "peau d'orange + rapid onset" = inflammatory; "single-file infiltrate, E-cadherin loss" = lobular; "scaly nipple" = Paget; "bloody single-duct discharge" = papilloma/DCIS; "clustered pleomorphic microcalcifications" = DCIS. These pattern-matches almost always direct the next-best-step answer.
Breast cancer management on Step 3 hinges on matching biology (ER/PR/HER2 ± germline status) and stage to a stepwise plan of triple-assessment diagnosis → biology-driven systemic therapy (often neoadjuvant for HER2+/TNBC ≥T2 or node+) → breast-conserving surgery + radiation or mastectomy with SLNB/ALND as indicated → multi-year endocrine therapy with adherence-focused survivorship care.
Board pearl: When stuck on a Step 3 breast cancer question, anchor on three axes — stage, receptor profile, and patient context (age, comorbidity, pregnancy, germline) — and the next-best-step answer almost always falls out of the intersection.