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Breast cancer — systemic therapy by subtype
Systemic therapy in breast cancer is set by three switches — hormone receptors, HER2 and a BRCA mutation — and by whether the disease is early (goal: cure) or metastatic (goal: long control).
Why it matters in the exam
This is the heaviest topic in the oncology bank. Stems give a patient with age, menopausal status, ER, PR, HER2, Ki-67 and stage, and ask about neoadjuvant, adjuvant, endocrine or metastatic treatment. Details appear on Oncotype DX, ovarian suppression (SOFT and TEXT), the tamoxifen-paroxetine interaction, the ECG before ribociclib, hyperglycaemia with alpelisib and interstitial lung disease with T-DXd.
The right way to answer always follows the same order: first identify the subtype by its receptors, then the stage and the risk, and only then choose between neoadjuvant therapy, upfront surgery or metastatic treatment. Many distractors are built on a correct drug for another subtype or on wrong timing.
Key points
- HR-positive: endocrine therapy is the backbone; chemotherapy only when genomic or clinical risk is high.
- HER2-positive: trastuzumab for one year; pertuzumab in high risk; T-DM1 for residual disease.
- Triple-negative from T2 or N1: neoadjuvant chemo-immunotherapy with pembrolizumab.
- Metastatic HR-positive: a CDK4/6 inhibitor with endocrine therapy first line.
- Key toxicities: QT with ribociclib, hyperglycaemia with alpelisib, ILD with T-DXd, the heart with anthracyclines and trastuzumab.
Summary table
| Subtype | Early disease | Metastatic disease |
|---|---|---|
| HR-positive, HER2-negative | Endocrine therapy for 5 to 10 years; chemotherapy by Oncotype DX and nodal status; abemaciclib or ribociclib in high risk | Aromatase inhibitor or fulvestrant with a CDK4/6 inhibitor; then by PIK3CA, AKT, ESR1 and BRCA |
| HER2-positive | From T2 or N1: chemotherapy with trastuzumab and pertuzumab before surgery; residual disease — T-DM1 | Taxane with trastuzumab and pertuzumab, then T-DXd |
| Triple-negative | From T2 or N1: chemotherapy with pembrolizumab before surgery; residual — capecitabine, or olaparib with BRCA | PD-L1 CPS of 10 or more: chemotherapy with pembrolizumab; then sacituzumab govitecan |
| BRCA1 or BRCA2 carrier | Adjuvant olaparib for one year in high risk | Olaparib or talazoparib |
| HER2-low (IHC 1+ or 2+ without amplification) | No change in treatment | T-DXd after prior therapy |
| Premenopausal high risk | Ovarian function suppression plus either tamoxifen or an aromatase inhibitor (SOFT/TEXT trials) | In metastatic disease: ovarian suppression is required for an aromatase inhibitor |
| Breast cancer during pregnancy | Surgery is possible in every trimester; anthracyclines from the second trimester; taxanes usually after | Trastuzumab, tamoxifen and radiotherapy wait until the baby is born |
Free exam questions
בת 38 נשאית BRCA1 נמצאה כסובלת מסרטן שד גרורתי לריאות ולכבד. מה מהבאים תומך במתן olaprib ?לעומת טיפול כימי לחולה זו (the question as examined, in Hebrew)
- א. התרופה נמצאה מעלה הישרדות כוללת במחקר פאזה 3
- ב. התרופה נמצאה כמעלה את שיעור התגובה לעומת טיפול כימי
- ג. התרופה נמצאה יותר יעילה מטיפול כימי במצבים של visceral crisis
- ד. התרופה נמצאה בעלת עדיפות בהעדר פיזור גרמי
מה נכון לגבי טיפלי בגלי חום ב חולת סרטן שד ש מקבלת טיפול משלים בטמוקסיפן ? (the question as examined, in Hebrew)
- א. Paroxetine הינו מעכב פוטנציאלי של CYP2D6 , ולכן לא מומלץ לשימוש יחד עם טמוקסיפן
- ב. Paroxetine הינו משפעל פוטנציאלי של הגן CYP2D6 , ולכן מומלץ לשימוש יחד עם טמוקסיפן
- ג. Paroxetine הינו משפעל פוטנציאלי של הגן CYP2D6, ולכן לא מומלץ לשימוש יחד עם. טמוקסיפן
- ד. Paroxetine הינו מעכב פוטנציאלי של הגן CYP2D6 , לכן מומלץ לשימוש יחד עם טמוקסיפן
In the full version for subscribers
- A simple algorithm
- Memory aid
- Exam traps
- 5 review cards
- Enough for IMLE
The full version is open to subscribers of: Oncology, Medical licensing exam (IMLE), General surgery.
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Sources
- NCCN Clinical Practice Guidelines in Oncology: Breast Cancer, 2026 — Systemic adjuvant and preoperative therapy; recurrent or stage IV disease
- ESMO Clinical Practice Guideline: Early breast cancer, 2024 — Diagnosis, treatment and follow-up
- ESMO Clinical Practice Guideline: Metastatic breast cancer, 2021, living guideline 2025 — Treatment by subtype
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.