Breast Invasive Ductal Carcinoma (IDC)

Invasive ductal carcinoma (IDC)—also termed invasive breast carcinoma of no special type (NST)—accounts for ~70–80% of invasive breast cancers. Curative pathways rely on complete local control (surgery ± radiation) plus subtype-guided systemic therapy. ER/PR and HER2 define major treatment branches; genomic assays refine chemotherapy need in selected HR+/HER2– early cases. Advanced disease is increasingly treated with targeted agents and antibody–drug conjugates. Management is multidisciplinary and benefits from tumor board review and upfront biomarker testing.

• ER (estrogen receptor) (common) — endocrine driver
• PR (progesterone receptor) (common) — luminal signaling; prognostic
• HER2 (ERBB2) amplification/overexpression (occasional) — growth factor receptor
• HER2-low phenotype (common) — ADC target phenotype (not HER2+)
• Ki-67 (variable) — proliferation index
• PIK3CA mutation (common) — PI3K pathway activation
• ESR1 mutation (occasional) — acquired endocrine resistance (LBD)
• AKT1 mutation / PTEN loss (occasional) — PI3K–AKT pathway activation
• TP53 mutation (common) — genome stability/tumor suppressor
• Androgen receptor (AR) expression (variable) — TNBC/luminal subset biology
• FGFR1 amplification (occasional) — endocrine resistance biology (subset of HR+)
• ERBB2 (HER2) activating mutation (non-amplified) (occasional) — kinase activation in HER2-non-amplified tumors
• PD-L1 (CPS) (variable) — immunotherapy biomarker (TNBC)
• Tumor-infiltrating lymphocytes (TILs) (variable) — immune prognostic marker (especially TNBC)
• BRCA1/2 (germline) / PALB2 (occasional) — homologous recombination deficiency
• TP53 (germline, Li-Fraumeni syndrome) (rare) — cancer predisposition; radiosensitivity
• CHEK2 / ATM (germline) (occasional) — moderate-penetrance susceptibility
• Homologous recombination deficiency (HRD) score/genomic scar (variable) — DNA repair deficiency signature
• NTRK1/2/3 fusion (rare) — tumor-agnostic driver
• TMB-high (rare) — immunotherapy biomarker
• MSI-H/dMMR (rare) — mismatch repair deficiency
• RB1 loss (occasional) — CDK4/6 inhibitor resistance biology
• CCNE1 amplification / high cyclin E (occasional) — cell-cycle bypass (CDK2 activation)
• Genomic assay: Oncotype DX Recurrence Score (common) — chemo benefit prediction in HR+/HER2–, node-negative (selected node-positive) early disease
• Genomic assays: MammaPrint / Prosigna (PAM50) / EndoPredict (occasional) — risk stratification in HR+/HER2– early disease
• HER3 (ERBB3) expression (variable) — ADC target (investigational)
• TROP-2 expression (common) — ADC target biology
• GATA3 / MAP3K1 mutations (common) — luminal lineage and favorable biology (context)

• ER/ESR1 signaling — lineage/emt
• HER2/ERBB2 signaling — growth factor
• PI3K–AKT–mTOR axis — metabolic
• CDK4/6 checkpoint — cell cycle
• DNA damage repair (HRD/BRCA/PALB2) — dna repair
• MAPK (RAS–RAF–MEK–ERK) — growth factor
• FGFR1 signaling — growth factor
• HER3/NRG1 axis — growth factor
• EMT and lineage plasticity (YAP/TEAD, FOXA1/GATA3 loss) — lineage/emt
• TGF-β signaling — invasion
• VEGF/HIF-1α angiogenesis — angiogenesis
• Tumor–immune microenvironment (TNBC) — immune
• Oxidative stress / NRF2 program — stress
• Metabolic rewiring (glycolysis–OXPHOS–lipid) — metabolic
• NOTCH / WNT / Hedgehog — developmental
• CXCL12–CXCR4 chemokine axis — invasion
• Integrin/FAK signaling — invasion

• Agents Database
• Protocols
• Alternative Therapies Guide
• Glossary
• Exercise & prehab
• Vitamin D (optimize levels)
• Fasting / FMD around chemo
• Melatonin
• Scalp cooling (cold caps)
• Hand–foot cryotherapy (frozen gloves/booties)
• Acupuncture
• Mindfulness/CBT-I
• Lymphedema prehab & compression (with PT/OT)
• Dietitian-guided protein & energy plan
• Yoga/Tai Chi (supervised)
• Omega-3 (EPA/DHA)
• Non-hormonal vaginal moisturizers + pelvic floor PT
• Probiotic/fermented foods strategy
• Photobiomodulation (low-level light) for RT skin/mucositis
• Adjuvant bisphosphonates (postmenopausal)

• rarity: Common; ~70–80% of invasive breast cancers.
• medianAge: Peak incidence in early 60s overall; TNBC tends to present younger (40s–50s), HER2+ skews slightly younger than HR+, and male IDC often presents in the late 60s–70s.
• annualIncidence: Common in women worldwide; uncommon in men. Population screening markedly increases early-stage detection and shifts treatment toward breast-conserving pathways.
• sex: Predominantly women; male breast cancer exists and is more often HR+/HER2–. Genetic evaluation is more frequently relevant in men (e.g., BRCA2).
• geographicVariation: Higher incidence in industrialized regions; rapid increases in transitioning countries. Access to screening and systemic therapy drives stage at diagnosis and survival disparities.
• riskFactors:
  • Age and family history (first-degree relative with breast/ovarian cancer).
  • Germline susceptibility: BRCA1/2, PALB2, CHEK2, ATM (and others).
  • High breast density (BI-RADS C/D) — both masks cancers and confers ~2–4× risk vs low density.
  • Prolonged estrogen exposure: early menarche, late menopause, nulliparity/late first pregnancy.
  • Hormone therapy (combined estrogen–progestin) — small but real increase in risk during use.
  • Prior chest radiation (e.g., mantle RT before age 30).
  • Lifestyle/metabolic: alcohol, obesity (post-menopausal), physical inactivity, insulin resistance.
  • Atypical ductal/lobular hyperplasia; LCIS as a risk marker (bilateral risk).
  • Pregnancy-associated breast cancer (during pregnancy or within ~1 year postpartum) has higher short-term relapse risk.
• prognosis: Excellent for many early-stage cases with modern multimodality therapy. Long-term outcomes hinge on subtype (HR+/HER2– vs HER2+ vs TNBC), nodal burden, grade, lymphovascular invasion, tumor size, margins, genomic assay risk (HR+/HER2–), and response to neoadjuvant therapy (pCR). Residual disease after neoadjuvant therapy guides effective response-adapted adjuvant options (e.g., T-DM1 for HER2+, capecitabine for TNBC).
• trends:
  • Neoadjuvant therapy standardizing in stage II–III HER2+ and TNBC to increase breast conservation and to enable response-adapted adjuvant therapy.
  • Genomic assays de-escalating adjuvant chemotherapy in selected HR+/HER2–, node-negative and select node-positive patients.
  • Targeted therapy expansion: CDK4/6, PI3K, AKT, and PARP agents moving earlier; ADCs (T-DXd, sacituzumab) reshaping metastatic care and being studied earlier.
  • HER2-low recognized as a therapeutically relevant metastatic phenotype (T-DXd) while not altering early-stage local therapy or classic HER2+ algorithms.
  • Radiation de-/re-calibration: broad adoption of hypofractionation and selectively 5-fraction regimens; refined nodal fields based on biology and response.
  • Axillary surgery de-escalation in select responders after neoadjuvant therapy (targeted axillary strategies) to reduce lymphedema without compromising control.
  • Equity focus: addressing subtype distribution and access disparities (e.g., higher TNBC proportion and later stage at diagnosis in some populations).

• IDC/NST morphology: infiltrating duct-forming carcinoma in a desmoplastic stroma; graded by Nottingham (tubule formation, nuclear grade, mitoses).
• Core IHC panel: ER, PR, HER2 (IHC ± ISH per ASCO/CAP), Ki-67 for proliferation context.
• E-cadherin retained (helps distinguish from classic lobular carcinoma with E-cadherin loss).
• Lymphovascular invasion (LVI) — adverse prognostic feature associated with nodal metastasis and recurrence.
• Tumor infiltrating lymphocytes (TILs) — prognostic in TNBC and predictive for neoadjuvant chemo/IO response.
• Basal cytokeratins (CK5/6, CK14) and EGFR can characterize basal-like biology within TNBC (prognostic context, trial eligibility).
• Special patterns (tubular, mucinous, medullary-like) often have distinct, sometimes more favorable behavior; verify because they can modify chemo decisions.
• HER2 scoring pitfalls: ensure accurate distinction between 0 vs 1+ to avoid misclassifying HER2-low eligibility in metastatic settings.

• Palpable, non-tender breast mass; firmness or architectural distortion.
• Screen-detected mammographic mass, calcifications, or architectural distortion; incidental MRI finding in high-risk screening.
• Axillary node enlargement or supraclavicular fullness.
• Nipple or skin changes: retraction/inversion, eczema-like areolar lesion, peau d’orange, non-lactational mastitis not resolving with antibiotics.
• Bloody or persistent unilateral nipple discharge (evaluate for intraductal pathology).
• Inflammatory breast cancer signs: rapid onset erythema/edema/warmth encompassing ≥1/3 of the breast.
• Male: subareolar mass with nipple retraction/ulceration; often HR+.

• Regional lymphatics: axillary (levels I–III), supraclavicular, and internal mammary basins.
• Distant hematogenous: bone (predominant in HR+; often lytic or mixed), lung, and liver across subtypes.
• Brain: more frequent in HER2+ and TNBC; requires low threshold for MRI with new neurologic symptoms.
• Chest wall/skin: local–regional recurrence along the scar or in prior radiation fields if control is incomplete.
• Lymphangitic carcinomatosis of the lungs in aggressive courses (progressive dyspnea, cough, hypoxemia).

• AJCC 8th uses anatomic TNM plus a prognostic stage that incorporates grade, ER/PR, and HER2 for early breast cancer.
• Use cTNM (clinical) for initial planning; pTNM for upfront surgery; ypTNM after neoadjuvant therapy. Document the ‘y’ prefix post-NAT.
• Clip the primary tumor and any biopsied positive node before neoadjuvant therapy to enable accurate post-NAT localization and targeted axillary dissection.
• Sentinel lymph node biopsy (SLNB) for clinically node-negative disease; dual tracer and retrieval of ≥2 SLNs improve accuracy.
• Micrometastasis (N1mi, 0.2–2.0 mm) is distinct from isolated tumor cells [N0(i+)]; management is individualized and often does not require completion ALND if breast-conserving RT is planned.
• Omission of ALND: Patients meeting Z0011-type criteria (T1–T2, cN0, 1–2 positive SLNs, lumpectomy + whole-breast RT) can avoid axillary dissection without compromising outcomes.
• If SLN positive outside Z0011 criteria, consider axillary RT as an alternative to ALND (AMAROS principles) depending on fields and comorbidity.
• Initially node-positive → NAT: use targeted axillary dissection (retrieve the clipped node + ≥2 additional SLNs). Aim for ≥3 nodes to keep the false-negative rate low.
• Residual nodal disease after NAT generally warrants ALND and/or comprehensive regional nodal irradiation; discuss in tumor board.
• Baseline staging scans (CT/PET, bone scan) are reserved for stage III or symptomatic stage I–II disease; avoid routine body imaging in asymptomatic early cases.
• Consider MRI for extent-of-disease mapping in dense breasts, multifocal disease, or when breast conservation is borderline.
• Lumpectomy margin standard: ‘no ink on tumor’ for invasive carcinoma. For pure DCIS, a 2 mm negative margin is preferred.
• Cavity-shave margins reduce re-excision rates and are reasonable when cosmesis allows.
• Pathologic complete response (pCR: ypT0/Tis ypN0) after NAT is a strong favorable prognostic marker in TNBC and HER2+ disease.
• Report Residual Cancer Burden (RCB) class after NAT when available; it refines prognosis and adjuvant decision-making.
• Use genomic assays (e.g., Oncotype DX) primarily in upfront-surgery HR+/HER2–, node-negative or select 1–3 node-positive cases to guide adjuvant chemo; they are not validated to guide therapy when substantial NAT has been given.

• CDK4/6 + endocrine therapy (AI or fulvestrant) is first-line standard for metastatic HR+/HER2–; choose agent by comorbidity (e.g., ribociclib OS data; abemaciclib diarrhea but less neutropenia).
• Post-CDK4/6 progression: re-profile (tumor or ctDNA). ESR1 mutation → SERD strategy (e.g., fulvestrant; oral SERDs where available).
• Alpelisib for PIK3CA-mutant HR+/HER2– after AI; start glucose monitoring and rash prophylaxis (non-sedating antihistamine).
• Capivasertib + fulvestrant improves outcomes in tumors with PI3K/AKT/PTEN alterations; counsel on diarrhea, rash, and hyperglycemia.
• Everolimus + exemestane restores endocrine sensitivity in some AI-resistant HR+; prevent stomatitis with dexamethasone mouthwash.
• Adjuvant abemaciclib for high-risk node-positive HR+/HER2– improves IDFS when added to endocrine therapy (strict eligibility).
• PARP inhibitors (olaparib/talazoparib) for gBRCA/PALB2: adjuvant (select high-risk HER2–) and metastatic; plan for anemia monitoring and contraception.
• Later-line ADCs in HR+/HER2–: sacituzumab govitecan after endocrine + targeted therapies; manage neutropenia/diarrhea proactively.
• HER2 sequence (metastatic): taxane + trastuzumab/pertuzumab → trastuzumab deruxtecan (T-DXd) → tucatinib + trastuzumab + capecitabine (brain-active) → other TKIs (neratinib/lapatinib) case-by-case.
• Residual disease after neoadjuvant HER2 therapy: switch to adjuvant T-DM1 to reduce recurrence risk.
• Extended adjuvant neratinib for high-risk HR+/HER2+ after trastuzumab (diarrhea prophylaxis mandatory) — center-specific use.
• T-DXd active in HER2-low (IHC 1+ or 2+/ISH–) metastatic after prior lines — emphasize ILD vigilance and early drug holds if symptomatic.
• Pembrolizumab for high-risk early TNBC (neoadjuvant + adjuvant) improves pCR/EFS; in metastatic TNBC, add to chemo for PD-L1–positive disease.
• Sacituzumab govitecan is a preferred later-line option in metastatic TNBC; early use of growth-factor support and loperamide reduces dose-limiting toxicity.
• gBRCA TNBC benefits from PARP inhibitors (metastatic) and adjuvant olaparib (select early).
• Platinum agents remain valuable in TNBC (particularly HRD contexts).
• HER2+ CNS disease: tucatinib-based regimens provide intracranial responses; integrate SRS/surgery with neuro-oncology.
• Oligometastatic scenarios (all subtypes): consider SBRT or surgery after systemic response in tumor board.
• Rare MSI-H/TMB-H/NTRK fusion can unlock tumor-agnostic immunotherapy/TRK inhibitors; screen with broad NGS when feasible.

• History/physical on a defined schedule; annual mammography of the conserved breast; avoid routine CT/PET/tumor markers in asymptomatic early-stage survivors.
• HER2 therapies: baseline ECHO/MUGA, then ~q3 months during active anti-HER2; hold/adjust per LVEF thresholds; manage HTN and CV risks.
• Anthracyclines: track cumulative dose; consider cardiology input for risk factors or borderline LVEF.
• CDK4/6: CBC q2–4 weeks initially (neutropenia), then space out; LFTs with abemaciclib/ribociclib; ECG/QTc with ribociclib (baseline, day 14 cycle 1, then each cycle early on).
• Alpelisib: fasting glucose/A1c at baseline and frequently early; start rash prophylaxis; monitor LFTs and lipids.
• Capivasertib: glucose, diarrhea, and rash checks each visit; reinforce antidiarrheals.
• Everolimus: oral-mucositis prophylaxis (steroid mouthwash), periodic CBC/LFTs; evaluate cough/fever for pneumonitis.
• PARP inhibitors: CBC q2–4 weeks initially (anemia/neutropenia); blood pressure and fatigue assessment.
• Sacituzumab govitecan: CBC before each dose (neutropenia), diarrhea plan with early loperamide; monitor LFTs.
• T-DXd: ILD/pneumonitis vigilance — prompt imaging for new cough/dyspnea/fever; hold at suspicion and involve pulmonology.
• Tucatinib regimens: monitor LFTs and diarrhea; counsel on hand-foot syndrome with capecitabine.
• Aromatase inhibitors: DEXA at baseline and periodically; vitamin D/calcium and weight-bearing exercise; consider adjuvant bisphosphonates (post-menopausal).
• Denosumab/zoledronic acid for metastases: dental clearance, calcium/vitamin D repletion, and hypocalcemia checks; ONJ precautions.
• Vaccinations (inactivated) per guidelines; assess HBV status prior to cytotoxic/IO when risk factors exist.
• Metastatic monitoring: cross-sectional imaging every 8–12 weeks (or per regimen) early, then extend if stable; symptom-triggered scans between visits.
• Low threshold for brain MRI with new neuro symptoms in HER2+ and TNBC; routine surveillance MRI is not standard without symptoms.

• Lymphedema program: prehab education, early PT/OT, compression fitting, and progressive weight training; prompt eval for arm swelling/tightness or axillary web syndrome.
• Shoulder mobility & scar management: early ROM, myofascial techniques, and desensitization to prevent frozen shoulder and chronic pain.
• Menopause symptom toolkit on endocrine therapy: non-hormonal options (SSRIs/SNRIs, gabapentin, clonidine), vaginal moisturizers/lubricants, and pelvic floor therapy; consider low-dose vaginal estrogen only after oncology review.
• Sexual health: address dyspareunia, libido, and body image; consider specialized pelvic PT and counseling.
• AI bone program: weight-bearing/resistance exercise, vitamin D/calcium, baseline and periodic DEXA; consider adjuvant bisphosphonates (postmenopausal) or denosumab with dental clearance.
• Cardio-oncology: manage BP, lipids, diabetes; baseline CV risk assessment before anthracyclines/HER2 therapy; lifestyle coaching for activity, weight, and sleep.
• Return-to-work & cognitive rehab: graded return plan, fatigue pacing, occupational therapy, and ‘chemo-brain’ strategies (sleep hygiene, cognitive exercises).
• Alopecia and neuropathy mitigation: scalp cooling during sensitive chemo; frozen gloves/booties during taxanes to reduce CIPN and nail toxicity.
• Stomatitis prevention: steroid mouthwash with everolimus; salt/bicarbonate rinses broadly; early dental issues triage to avoid ONJ when on bone agents.
• GI playbooks: diarrhea (abemaciclib/capecitabine/sacituzumab) start loperamide early; nausea bundles with evidence-based antiemetics; constipation prevention with opioids/antiemetics.
• Pulmonary vigilance: new cough/dyspnea/fever on T-DXd or everolimus → urgent ILD/pneumonitis evaluation and drug hold.
• Dermatologic care: alpelisib/capivasertib rash prophylaxis (non-sedating antihistamines), urea-based emollients; HFS care on capecitabine.
• Metabolic monitoring: proactive glucose/A1c and dietitian input with alpelisib/capivasertib; avoid unsupervised fasting in underweight/sarcopenic patients.
• Multimodal analgesia: NSAIDs/acetaminophen, neuropathic agents (duloxetine for CIPN), interventional options when needed; early palliative/supportive care improves QoL.
• Sleep, anxiety, and mood: CBT-I, mindfulness, exercise; screen for depression/PTSD and treat promptly.
• Vaccination plan: inactivated vaccines per guidelines; avoid live vaccines during cytotoxic therapy/biologics; consider HBV screening in at-risk patients.
• Port care: educate on infection/DVT signs; coordinate holds around procedures (anticoagulants, bone agents).
• Navigation and financial counseling: transportation, work leave, medication access, and clinical trial matching to reduce care gaps.

• CDK4/6 inhibitors: avoid strong CYP3A4 inhibitors/inducers (e.g., azoles, clarithromycin, rifampin, St. John’s wort); consider dose adjustments and avoid grapefruit/Seville orange.
• Ribociclib: QT-prolonging combinations (certain antiemetics, macrolides, fluoroquinolones, antipsychotics) require ECG/electrolyte monitoring or avoidance.
• Tamoxifen: avoid strong CYP2D6 inhibitors (paroxetine, fluoxetine); consider alternatives (venlafaxine) for hot flashes.
• Alpelisib: uncontrolled diabetes or history of DKA warrants caution; monitor glucose/ketones; institute rash prophylaxis; hold SGLT2 inhibitors around surgery.
• Capivasertib: monitor glucose and rash; caution with strong CYP3A modulators.
• Everolimus: infection risk and stomatitis — use oral care bundle; hold for non-infectious pneumonitis; avoid live vaccines.
• PARP inhibitors: avoid in pregnancy; monitor for anemia; caution with strong P-gp/CYP interactions per label.
• T-DXd: ILD/pneumonitis risk — hold at first respiratory symptoms; permanently discontinue for grade ≥2 ILD; avoid if active ILD.
• T-DM1: hepatotoxicity and thrombocytopenia — monitor LFTs/platelets; avoid concomitant hepatotoxins when possible.
• Anthracyclines with concurrent trastuzumab: avoid concurrent administration due to compounded cardiotoxicity; ensure adequate washout and cardiac monitoring.
• Capecitabine: screen for clinically suspected DPD deficiency; severe deficiency is a contraindication.
• Sacituzumab govitecan: higher neutropenia risk with UGT1A1*28 — consider closer monitoring and growth-factor support.
• Bisphosphonates/denosumab: obtain dental clearance before initiation; avoid elective invasive dental procedures during therapy to lower ONJ risk; ensure calcium/vitamin D repletion.
• Immediate reconstruction: coordinate with radiation to avoid implant loss/complications; consider delaying or using autologous options case-by-case.
• Avoid live vaccines during cytotoxic therapy/biologics; use inactivated vaccines on schedule; evaluate HBV status when immunosuppression is planned.
• Most systemic agents (cytotoxics, targeted therapies, ADCs) are teratogenic — avoid during pregnancy and breastfeeding; use effective contraception during and for the labeled washout period after treatment.

• Fever ≥100.4°F (38.0°C) during chemo or any fever with rigors/confusion — go to the ER now.
• Acute chest pain, new oxygen saturation <92% at rest, or sudden shortness of breath — call emergency services.
• New focal weakness, severe back pain with leg symptoms, or loss of bowel/bladder control — spine emergency.
• Severe, worst-ever headache, confusion, or seizure — neurologic emergency.
• Persistent vomiting (>4 episodes in 6 hours) or inability to keep liquids down >12 hours — risk of dangerous dehydration.
• Severe allergic infusion reaction (wheezing, facial/tongue swelling, hives, dizziness) — anaphylaxis protocol.
• Bright red blood in stool, black tarry stools, or uncontrolled bleeding — GI/hematologic emergency.
• New or rapidly worsening cough/dyspnea on T-DXd — hold drug and seek urgent evaluation for ILD.
• Blood glucose ≥300 mg/dL with ketones or DKA symptoms (abdominal pain, rapid breathing, confusion) — urgent care now.
• Syncope, palpitations with dizziness, or prolonged QT concerns on ribociclib — urgent evaluation.
• Severe chest pressure, new edema/orthopnea on HER2 therapy — possible heart failure; urgent assessment.
• Severe abdominal pain with guarding or jaundice — urgent evaluation for biliary obstruction or hepatic crisis.

• New or worsening breast/chest wall pain, swelling, redness, warmth, or drainage.
• Incision healing concerns, seroma, or restricted shoulder motion — ask about early PT/OT.
• Arm swelling, heaviness, or tightness — possible lymphedema vs DVT; ask about compression and duplex ultrasound if asymmetric.
• New or persistent bone pain, headaches, dizziness, or neuropathy symptoms.
• Diarrhea on abemaciclib that persists despite loperamide or is ≥4 stools/day over baseline.
• Rash, rising glucose, or mouth sores on alpelisib; ask about glucose checks and rash prophylaxis.
• Mouth ulcers, rash, cough, or low-grade fever on everolimus — consider stomatitis prophylaxis and pneumonitis workup.
• New cough or shortness of breath on T-DXd — even mild — discuss ILD workup promptly.
• Palpitations, edema, or reduced exercise tolerance on HER2 therapy — arrange cardiac check (ECHO/MUGA).
• Visual changes, severe leg cramps, or new calf pain on tamoxifen — discuss ocular exam and DVT evaluation.
• Planned dental extraction/implant while on bisphosphonate/denosumab — coordinate to minimize ONJ risk.
• Skin reaction, new cough after radiation, or concern for radiation recall with subsequent chemo — review medications and timing.
• Any new prescription, OTC, or herbal supplement (CYP3A4/QT interactions are common).
• Upcoming surgery or invasive procedures — confirm holds (e.g., anticoagulants) and timing around therapy.
• Hot flashes, arthralgia, sexual health concerns, sleep disturbance, mood changes — adjust endocrine therapy supports and referrals.

• Diagnostic mammography/ultrasound ± MRI for local assessment.
• Staging CT/bone scan or PET/CT for stage III/IV or symptoms.
• Brain MRI for neurologic symptoms or high-risk biology (HER2+, TNBC).
• Annual mammogram for conserved breast; tailored imaging otherwise.

• Stage (tumor size, nodal burden, metastasis).
• Subtype (TNBC and HER2+ historically higher risk; modern HER2 therapy improves outcomes).
• Grade, lymphovascular invasion, margins.
• Pathologic complete response (pCR) after neoadjuvant therapy (TNBC/HER2+).
• Genomic assay score in HR+/HER2– early disease.

• Curative-intent for localized disease with surgery + RT and tailored systemic therapy.
• Response-adapted plans after neoadjuvant therapy (adjuvant T-DM1, capecitabine, or pembrolizumab as indicated).
• Metastatic: disease control with quality-of-life preservation; targeted and ADC sequences.
• Trial-first for molecular matches or novel ADC/IO combinations.

• Pain control, bone-stabilizing agents for skeletal mets (zoledronic acid/denosumab).
• Brain mets: local therapy (SRS), systemic HER2-active agents for HER2+.
• Ascites/pleural effusion management when present.
• Fatigue, mood, sleep, and cognitive supports.

• AC-T (doxorubicin/cyclophosphamide → paclitaxel) — early/high-risk (Common adjuvant/neoadjuvant backbone; monitor cardiotoxicity and neuropathy.)
• TC (docetaxel/cyclophosphamide) — early (Non-anthracycline option; consider in lower cardiac reserve.)
• THP / TCHP (taxane ± carboplatin + trastuzumab/pertuzumab) — HER2+ neoadjuvant (Preferred for stage II–III HER2+; adapt adjuvant based on pCR/residual disease.)
• Capecitabine — post-neoadjuvant TNBC residual (Improves outcomes in residual TNBC after neoadjuvant chemo.)

• ER/PR/HER2/Ki-67 (core IHC ± ISH) — Subtype and systemic backbone selection.
• Genomic assay (Oncotype DX / MammaPrint in eligible HR+/HER2–) — Adjuvant chemo decision support.
• NGS panel (tumor; ± ctDNA at progression) — PIK3CA/ESR1/AKT1/PTEN/NTRK and TMB.
• Germline testing (BRCA1/2, PALB2, etc.) — PARP inhibitors; surgical/family planning.
• PD-L1 CPS (TNBC) — Chemo-IO in early high-risk and metastatic TNBC.
• ECHO/MUGA baseline — Safe use of HER2-directed therapy.

• ESR1 mutation oral SERD (elacestrant, camizestrant, giredestrant)
• CDK4/6 beyond progression strategies
• CDK2 inhibitor cyclin-E–high HR+
• PIK3CA alpelisib combinations
• AKT1/PTEN/PI3K capivasertib combinations
• mTOR combinations everolimus endocrine-resistant
• PARP inhibitor BRCA PALB2 adjuvant metastatic
• ATR/CHK1/WEE1 inhibitor HRD breast cancer
• TROP-2 ADC sacituzumab earlier-line HR+ and TNBC
• TROP-2 ADC datopotamab deruxtecan TNBC HR+
• HER3 ADC patritumab deruxtecan HR+
• HER2-low trastuzumab deruxtecan escalation/de-escalation
• immunotherapy TNBC PD-L1 pembrolizumab combinations
• TIL therapy TNBC
• STING/TGF-β modulators immune-excluded TNBC
• brain metastases HER2 tucatinib SRS integration
• oligometastatic SBRT consolidation breast cancer
• ovarian suppression premenopausal HR+ intensification
• ctDNA MRD escalation de-escalation trials
• liquid biopsy ESR1 PIK3CA-guided therapy switch
• FGFR1 amplified HR+ FGFR inhibitor
• HER2 activating mutation non-amplified TKI basket

• Oral SERD in ESR1-mutant HR+ after CDK4/6.
• Next-gen CDK inhibitors post-CDK4/6 progression.
• PI3K/AKT pathway combos (alpelisib/capivasertib) sequencing.
• ADC head-to-head or biomarker-directed selection (TROP-2, HER2-low).
• ctDNA MRD-guided escalation/de-escalation studies.

Early-stage survivorship: H&P every 3–6 months for 3 years, then every 6–12 months to year 5, then annually; annual mammography if breast-conserving. On therapy: labs and toxicity checks per regimen; ECHO/MUGA every ~3 months on HER2 therapy. Imaging for metastatic disease every 8–12 weeks initially, then tailor to tempo and symptoms.

• Coordinate reconstruction timing with RT plans.
• Map nadirs and schedule dental work/procedures outside neutropenic windows.
• Space contrast CT and nephrotoxic meds around anthracycline/cyclophosphamide days.
• Pre-book cardiac imaging to avoid HER2-therapy delays.

• High-dose antioxidants ↔ infusion days for ROS-dependent chemo.
• Strong CYP3A4 modulators ↔ CDK4/6 inhibitors without review.
• QT-prolongers ↔ ribociclib without ECG/electrolyte monitoring.

• Protein targets ~1.2–1.5 g/kg/day during treatment when feasible.
• Manage AI-related weight, bone health, and glucose/lipid changes.
• Alcohol moderation; hydration to manage chemo side effects.
• Food-safety counseling during neutropenia.

• Ports: infection vigilance; arm swelling → evaluate for catheter DVT.
• Breast implants/expanders: coordinate with RT planning.
• Cardiac devices: confirm MRI and RT constraints.

• Anthracyclines: cardiotoxicity—baseline and periodic LVEF.
• Taxanes: neuropathy; consider cryotherapy and dose adjustments.
• Trastuzumab/pertuzumab: cardiomyopathy—ECHO/MUGA q3 months.
• T-DM1: thrombocytopenia/transaminitis—CBC/LFTs.
• T-DXd: ILD/pneumonitis—educate about cough/dyspnea; hold and evaluate promptly.
• Abemaciclib: diarrhea—early loperamide plan; CBC/LFTs.
• Ribociclib: QT prolongation—ECG/electrolytes at baseline and on therapy.
• Alpelisib: hyperglycemia/rash—fasting glucose, A1c, dermatologic prophylaxis.
• Everolimus: stomatitis—steroid mouthwash prophylaxis; infection vigilance.
• PARP inhibitors: anemia/thrombocytopenia—CBC monitoring.
• Capecitabine: hand–foot syndrome—dose holds and supportive care per grade.

• trial-eligibility
• trial-vs-standard
• toxicity-tolerance
• monitoring-plan
• goals-of-care
• adjunct-timing
• genomic-assay
• breast-conservation
• reconstruction
• cardio-oncology
• bone-health
• endocrine-duration
• ctdna-trending

• Optimal sequencing of targeted agents after CDK4/6 exposure.
• Best strategies for endocrine-resistant ESR1-mutant disease beyond current SERDs.
• Definitive role of ctDNA MRD to escalate/de-escalate adjuvant therapy.
• Selection between ADCs in later-line HR+ disease.

• Which subtype do I have (luminal A/B, HER2+, TNBC) and what is our best curative plan?
• Do I need neoadjuvant therapy to increase breast conservation and tailor adjuvant options by response (pCR vs residual)?
• Will a genomic assay (e.g., Oncotype DX) change whether I need chemotherapy?
• Am I a candidate for lumpectomy with oncoplastic techniques, or is mastectomy preferable?
• Do I qualify for Z0011-type omission of axillary dissection or targeted axillary dissection after neoadjuvant therapy?
• What radiation fields (breast/chest wall, nodes) and schedule (hypofractionation, 5-fraction, boost) fit my case?
• How does reconstruction timing interact with radiation to optimize outcomes?
• Am I eligible for CDK4/6, PI3K/AKT/mTOR, PARP inhibitors, or ADCs (T-DXd, sacituzumab)?
• Should we test for ESR1/PIK3CA/AKT1/PTEN through ctDNA now or at progression to direct targeted therapy?
• What is our cardiac monitoring plan on HER2 therapy or anthracyclines?
• How will we detect and manage ILD risk on T-DXd and stomatitis on everolimus?
• What’s the plan for diarrhea on abemaciclib/capecitabine and hyperglycemia/rash on alpelisib/capivasertib?
• Should I pursue fertility preservation before chemo, and how would ovarian suppression fit in?
• Can I pause endocrine therapy in the future for pregnancy under supervision?
• How will we prevent lymphedema and bone loss, and what are my DEXA and bone-agent plans?
• Which clinical trials fit my biomarkers (ESR1, PIK3CA, BRCA/PALB2, HER2-low)?
• What is our imaging and clinic follow-up cadence during and after treatment?
• What support do you offer for fatigue, cognitive changes, sexual health, and return to work?
• Can I use scalp cooling and hand–foot cryotherapy with my regimen?

• https://clinicaltrials.gov/search?cond=breast+invasive+ductal+carcinoma
• https://www.cancer.gov/about-cancer/treatment/clinical-trials/search
• https://www.esmo.org/guide-lines/breast-cancer

1. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer

   NCCN

   • Subtype-driven systemic therapy
   • Radiation fields
   • Survivorship surveillance

2. ESMO Guidelines: Early and Metastatic Breast Cancer

   ESMO

   • Neoadjuvant strategies (TNBC, HER2+)
   • Targeted therapy sequences
   • ADC use

3. ASCO Guidelines & St Gallen Consensus

   ASCO

   • Genomic assay use in HR+/HER2–
   • Endocrine therapy duration
   • CDK4/6, PI3K, AKT recommendations

• Alternative Therapies Guide
• Agents Database
• Protocols

• Educational resource; not medical advice. Coordinate decisions with breast oncology, surgery, radiation oncology, genetics, and cardio-oncology as needed.