Key points
- Breast cancer is the most common cancer in women worldwide and accounted for about 11.6% of all cancers diagnosed in 2022 [1].
- The US Preventive Services Task Force (USPSTF) recommends mammography every two years for all women aged 40 to 74 [2].
- Treatment is chosen according to the molecular subtype (hormone receptors, HER2) and the stage of the disease; there is no single treatment for everyone [3, 4].
- In the early stages, breast-conserving surgery plus radiotherapy gives the same long-term survival as mastectomy [5].
- New drugs such as immunotherapy and antibody–drug conjugates (ADCs) have significantly improved survival in several subtypes in recent years [6, 7, 8].
What is breast cancer?
Breast cancer develops when cells in the breast tissue grow out of control. Most invasive breast cancers arise from the milk ducts (invasive carcinoma of no special type, formerly called “ductal”) or from the milk-producing lobules (lobular carcinoma) [3]. In some patients, the abnormal cells have not yet broken through the wall of the duct; this is called “carcinoma in situ” (DCIS), a pre-invasive stage [3].
According to GLOBOCAN estimates, breast cancer was the most common cancer and the leading cause of cancer death in women in 2022 [1]. Even so, thanks to early detection and the treatment advances of recent decades, most women diagnosed at an early stage receive curative treatment and go on to live long, good-quality lives [3].
Signs and symptoms
In its early stages, breast cancer often causes no symptoms, and many cases today are found through screening mammography [3]. Symptoms that should always be reported to a doctor:
- A new lump or thickening in the breast or armpit
- A change in the size or shape of the breast
- Dimpling, puckering, thickening or redness of the breast skin (an “orange peel” appearance)
- A newly inverted nipple, a sore or scaling on the nipple, or bloody nipple discharge
- Swelling of part of the breast or armpit, even if no lump can be felt
When should I see a doctor?
Discuss any of the changes above in the breast or armpit with a doctor. Most breast lumps are benign (such as cysts or fibroadenomas). Even so, any new change that lasts more than a few weeks, especially after your period has ended, should be checked by a doctor. Seeing a doctor early increases the chance of simpler and more successful treatment.
Risk factors, prevention and screening
Having one or more risk factors does not mean that a person will definitely get the disease; many women with breast cancer have no known risk factor other than “being a woman” and “getting older” [3]. The most important risk factors are [3]:
- Factors that cannot be changed: increasing age, a family history of breast or ovarian cancer, inherited genetic mutations (especially BRCA1 and BRCA2), dense breast tissue, an early start of menstruation or a late menopause, and a history of chest radiotherapy at a young age.
- Factors that can be changed: obesity after menopause, alcohol use, physical inactivity, and long-term use of combined hormone therapy after menopause.
Keeping a healthy weight, regular physical activity, avoiding alcohol and breastfeeding are among the steps associated with a lower risk [3].
In a large prospective study, the cumulative risk of breast cancer by age 80 was estimated at about 72% for carriers of a BRCA1 mutation and about 69% for carriers of a BRCA2 mutation [9]. If several people in your family have had breast or ovarian cancer, or if breast cancer occurred at a young age or in a man in the family, talk to your doctor about genetic counseling and testing. The result affects both screening and prevention for family members and the choice of treatment (such as PARP inhibitor drugs) [4, 10].
Screening and early detection
In its 2024 recommendation, the US Preventive Services Task Force (USPSTF) recommended mammography every two years for all women aged 40 to 74 (grade B recommendation) [2]. The task force found the evidence insufficient to recommend supplemental screening with ultrasound or MRI in women with dense breasts who have had a negative mammogram [2].
Women at high risk (such as carriers of BRCA mutations or women who had chest radiotherapy at a young age) usually need a special program that includes starting screening earlier and annual MRI [4].
Diagnosis and staging
Diagnostic pathway for breast cancer
- 1
Clinical examination
Examination of the breasts and of the lymph nodes in the armpits and above the collarbones by a doctor.
- 2
Breast imaging
Diagnostic mammography and ultrasound of the breast and armpit; breast MRI in specific cases [4].
- 3
Needle biopsy (core biopsy)
Removal of a small tissue sample under imaging guidance; the only definitive way to diagnose cancer [4].
- 4
Pathology and marker testing
Determining the histologic type, the tumor grade and the status of the estrogen receptor (ER), progesterone receptor (PR), HER2 and the Ki-67 proliferation index [4].
- 5
Staging
Determining tumor size (T), lymph node involvement (N) and distant metastasis (M). In more advanced locoregional disease, or when symptoms are present, whole-body imaging (CT or PET-CT and a bone scan) is performed [4].
- 6
Genetic counseling and multidisciplinary team meeting
BRCA1/2 genetic testing if the criteria are met; then a treatment plan is drawn up at a joint meeting of the surgeon, oncologist, radiation oncologist, radiologist and pathologist [4].
Molecular subtypes
Not all breast cancers are the same. The receptors present on the cancer cells determine how the tumor behaves and which drugs work best [3]. The most common subtype is hormone receptor-positive, HER2-negative tumors [3]. In recent years, a new group called HER2-low (low HER2 expression) — that is, an immunohistochemistry score of 1+ or 2+ with a negative ISH test — has also been recognized as a treatment target [11].
| Subtype | Features | Main systemic treatments |
|---|---|---|
| Hormone receptor-positive / HER2-negative | The most common subtype; estrogen-dependent growth [3] | Hormone therapy (tamoxifen or an aromatase inhibitor); in high-risk cases, adding a CDK4/6 inhibitor (abemaciclib and, in some patients, ribociclib) [12, 13]; in metastatic disease, hormone therapy plus palbociclib or abemaciclib in the first line [23, 24, 26] and, in later lines, fulvestrant plus palbociclib or exemestane plus everolimus [29, 30]; chemotherapy based on the risk of recurrence and genomic tests [14] |
| HER2-positive | High expression of the HER2 protein; excellent response to anti-HER2 drugs [3] | Trastuzumab and pertuzumab with chemotherapy; for residual disease after preoperative treatment, antibody–drug conjugates [7, 15] |
| HER2-low | IHC 1+ or 2+ with negative ISH; previously regarded as “HER2-negative” [11] | Trastuzumab deruxtecan (T-DXd) in metastatic disease after prior hormone therapy or chemotherapy [11, 28] |
| Triple-negative (TNBC) | Lacks ER, PR and HER2; usually more aggressive and more common in younger women and in BRCA1 carriers [3] | Chemotherapy plus pembrolizumab in stages II and III [6, 16]; in advanced PD-L1-positive disease (CPS ≥10), chemotherapy plus pembrolizumab [25] and the newer combination of sacituzumab govitecan plus pembrolizumab [17]; in germline BRCA mutation carriers, olaparib [10, 27] |
The final choice of treatment depends on the stage of the disease, menopausal status, other medical conditions and the patient’s preferences, and should be decided by a multidisciplinary team.
Treatment by stage
Pillars of treatment
Surgery
Removal of the tumor while preserving the breast (lumpectomy) or removal of the whole breast (mastectomy), together with assessment of the armpit lymph nodes (usually by sentinel lymph node biopsy) [4].
Radiation therapy
Usually after breast-conserving surgery, and after mastectomy in high-risk patients (for example, those with lymph node involvement), to reduce the risk of local recurrence [4].
Chemotherapy
Before surgery (neoadjuvant) to shrink the tumor and gauge its response, or after surgery. In HR-positive tumors without lymph node involvement, genomic tests such as Oncotype DX show who will not benefit from chemotherapy [14].
Hormone therapy
For hormone receptor-positive tumors, usually for 5 to 10 years; in high-risk patients with lymph node involvement, combined with the CDK4/6 inhibitor abemaciclib, which, in addition to reducing recurrence, has also improved overall survival [4, 12]; ribociclib is another option, whose trial included a broader group of patients with stage II–III disease [13].
Targeted therapy
Anti-HER2 drugs (trastuzumab, pertuzumab and antibody–drug conjugates such as T-DM1 and T-DXd) [7, 15], PARP inhibitors such as olaparib for BRCA mutation carriers [10, 27], everolimus with hormone therapy in hormone receptor-positive metastatic disease [29] and, in tumors with PIK3CA mutations, newer drugs targeting the PI3K pathway [18].
Immunotherapy
Immune checkpoint inhibitors, especially pembrolizumab with chemotherapy in high-risk early-stage triple-negative breast cancer and in advanced PD-L1-positive disease [6, 25].
Treatment overview by stage
- 1
Stage 0 (DCIS)
Surgery (usually breast-conserving) and, in many patients, radiotherapy; in hormone receptor-positive DCIS, hormone therapy may also be offered [4].
- 2
Stages I and II (early)
Surgery and, if needed, radiotherapy, followed by systemic treatment matched to the subtype. In HER2-positive or triple-negative tumors larger than about 2 cm or with lymph node involvement, systemic treatment before surgery is often preferred [4].
- 3
- 4
Stage IV (metastatic)
The goal is long-term disease control while preserving quality of life. Treatment is chosen according to the subtype: in HR-positive/HER2-negative disease, usually hormone therapy plus palbociclib or abemaciclib [23, 24, 26]; in HER2-positive disease, anti-HER2 drugs combined with chemotherapy [8, 21, 26]; and in PD-L1-positive triple-negative disease, chemotherapy plus pembrolizumab [25]. Treatment continues in successive lines, and tumor mutations (BRCA, ESR1, PIK3CA) and the level of HER2 expression determine the next options [18, 19, 26, 27, 28].
What should I do after a diagnosis?
Frequently asked questions
Is breast cancer hereditary?
Most breast cancers are not hereditary, but some are linked to inherited genetic mutations such as BRCA1 and BRCA2, which greatly increase the risk [3, 9]. If several of your relatives have had breast or ovarian cancer, talk to your doctor about genetic counseling. Full answer: Is cancer hereditary? (Persian)
Can men get breast cancer too?
Yes, although it is rare. Men should also see a doctor if they notice a lump or a change in the breast area; breast cancer in a man, especially together with a family history, is one of the reasons for genetic testing.
Is mammography dangerous?
Mammography uses a very small amount of radiation. After reviewing the evidence, the USPSTF concluded that the benefits of mammography every two years in women aged 40 to 74 outweigh its possible harms (such as false-positive results) [2].
Is removing the whole breast (mastectomy) safer than breast-conserving surgery?
For suitable tumors, breast-conserving surgery plus radiotherapy gives the same long-term survival as mastectomy; in a trial with 20 years of follow-up, the death rates in the two groups were almost identical (41.7% vs 41.2%) [5]. The choice of procedure depends on the size of the tumor, the size of the breast, genetics and your own preference.
Do all patients need chemotherapy?
No. In many women with hormone receptor-positive, HER2-negative tumors without lymph node involvement, genomic tests such as Oncotype DX help identify those who will not benefit from chemotherapy. In the TAILORx trial, in the intermediate-score group, hormone therapy alone was not inferior to chemotherapy plus hormone therapy for invasive disease-free survival, although some benefit from chemotherapy was seen in some women aged 50 or younger [14].
Can metastatic breast cancer be treated?
Metastatic breast cancer usually cannot be completely eradicated, but today many patients live for years with a good quality of life thanks to successive and targeted treatments. For example, in HER2-positive disease, median progression-free survival with new first-line treatment has passed 40 months [8]. Full answer: Is breast cancer curable? (Persian)
Evidence and recent advances (for physicians)
For physicians
Early breast cancer
For physicians
| Trial | Population | Intervention | Main result |
|---|---|---|---|
| KEYNOTE-522 [6, 16] | Stage II–III TNBC | Pembrolizumab + carboplatin-containing neoadjuvant chemotherapy, then adjuvant pembrolizumab | pCR: 64.8% vs 51.2%; 60-month overall survival: 86.6% vs 81.7% (P=0.002; final analysis, median follow-up 75.1 months) |
| KATHERINE [15, 22] | HER2-positive with residual disease after neoadjuvant therapy | T-DM1 vs trastuzumab | Three-year iDFS 88.3% vs 77.0%; HR 0.50; 7-year overall survival 89.1% vs 84.4% (HR 0.66; final analysis, median follow-up 8.4 years) |
| DESTINY-Breast05 [7] | High-risk HER2-positive with residual disease | T-DXd vs T-DM1 | Three-year iDFS 92.4% vs 83.7%; HR 0.47 |
| OlympiA [10] | High-risk HER2-negative with a germline BRCA1/2 mutation | One year of olaparib vs placebo | iDFS: HR 0.65; 6-year overall survival 87.5% vs 83.2% (HR 0.72; median follow-up 6.1 years) |
| monarchE [12] | High-risk, node-positive HR+/HER2− | Two years of abemaciclib + hormone therapy | Seven-year iDFS 77.4% vs 70.9%; overall survival: HR 0.842, i.e., a 15.8% reduction in the risk of death (7-year 86.8% vs 85.0%) |
| CREATE-X [31] | HER2-negative with residual disease after neoadjuvant chemotherapy | Adjuvant capecitabine vs standard treatment without capecitabine | Triple-negative subgroup: 5-year disease-free survival 69.8% vs 56.1% (HR 0.58); overall survival 78.8% vs 70.3% |
| NATALEE [13] | Stage II–III HR+/HER2− (including high-risk N0) | Three years of ribociclib + a nonsteroidal aromatase inhibitor | iDFS: HR 0.716; 5-year absolute difference 4.5%; overall survival not yet conclusive (HR 0.800) |
iDFS: invasive disease-free survival; pCR: pathologic complete response; HR: hazard ratio.
Advanced triple-negative breast cancer
In untreated advanced disease with PD-L1 CPS ≥10, adding pembrolizumab to chemotherapy (paclitaxel, nab-paclitaxel or gemcitabine–carboplatin) in KEYNOTE-355 increased median overall survival from 16.1 to 23.0 months (HR 0.73); with CPS between 1 and 10, this benefit was not significant [25]. In HER2-negative metastatic disease with a germline BRCA mutation, olaparib in OlympiAD increased median PFS from 4.2 to 7.0 months compared with standard chemotherapy (HR 0.58) [27]. A newer combination, sacituzumab govitecan plus pembrolizumab, improved median PFS compared with chemotherapy plus pembrolizumab in untreated advanced PD-L1-positive disease in the ASCENT-04/KEYNOTE-D19 trial (11.2 vs 7.8 months; HR 0.65), with fewer treatment discontinuations due to adverse events (12% vs 31%); overall survival data are still immature [17].
Advanced HER2-positive and HER2-low breast cancer
In the first-line metastatic setting, the THP regimen (taxane, trastuzumab, pertuzumab) is the preferred approach for most patients [21, 26]. In DESTINY-Breast09, first-line T-DXd plus pertuzumab increased median PFS to 40.7 months vs 26.9 months with THP (HR 0.56) [8]; however, because of the risk of interstitial lung disease and the absence of crossover in this trial, the NCCN guideline (version 4.2026) lists T-DXd plus pertuzumab among “other recommended options” [21]. In the second line, trastuzumab deruxtecan was superior to T-DM1 in DESTINY-Breast03, and in the long-term analysis (median follow-up 41 months), investigator-assessed median PFS was 29.0 vs 7.2 months (HR 0.30) and median overall survival 52.6 vs 42.7 months (HR 0.73) [20]. In HER2-low metastatic disease previously treated with chemotherapy, DESTINY-Breast04 showed improved PFS (9.9 vs 5.1 months) and overall survival (23.4 vs 16.8 months) with T-DXd [11]; and in HR-positive HER2-low or HER2-ultralow disease after hormone therapy and before chemotherapy, DESTINY-Breast06 increased median PFS in the HER2-low group from 8.1 to 13.2 months (HR 0.62) [28].
Interstitial lung disease (ILD)/pneumonitis is the most important adverse event of T-DXd: drug-related ILD was reported in 9.6% of patients in DESTINY-Breast05 (vs 1.6% with T-DM1) and in 12.1% in DESTINY-Breast09, and close respiratory monitoring is essential [7, 8].
Advanced HR-positive / HER2-negative breast cancer
In metastatic disease, the standard first-line treatment is hormone therapy plus a CDK4/6 inhibitor [26]: in PALOMA-2, adding palbociclib to letrozole increased median PFS from 14.5 to 24.8 months (HR 0.58) [23], and in MONARCH 3, adding abemaciclib to a nonsteroidal aromatase inhibitor reduced the risk of progression or death (HR 0.54) [24]. Ribociclib with letrozole in MONALEESA-2 also increased median overall survival to 63.9 vs 51.4 months (HR 0.76) [32]. After progression on hormone therapy, common options include fulvestrant plus palbociclib (PALOMA-3: median PFS 9.2 vs 3.8 months; HR 0.42) [30] and exemestane plus everolimus (BOLERO-2: 6.9 vs 2.8 months; HR 0.43) [29]; olaparib in germline BRCA mutation carriers [27] and trastuzumab deruxtecan in HER2-low or HER2-ultralow tumors [28] are also options.
Among newer targeted approaches, monitoring of circulating tumor DNA (ctDNA) in SERENA-6 showed that switching early to camizestrant, an oral estrogen receptor degrader, as soon as an ESR1 mutation emerged and before clinical progression increased median PFS from 9.2 to 16.0 months (HR 0.44) [19]. In addition, in PIK3CA-mutated tumors that recurred during or shortly after adjuvant hormone therapy, adding inavolisib to palbociclib and fulvestrant roughly doubled PFS compared with palbociclib and fulvestrant (15.0 vs 7.3 months; HR 0.43) [18].
Treatment regimens and dosing (for physicians)
Treatment regimens and doses: index22 regimens
These notes apply to all the regimens below that contain the drug concerned and are not repeated in the note of each regimen.
- Paclitaxel: per the label, premedication with a corticosteroid (e.g., dexamethasone 20 mg orally about 12 and 6 hours before), diphenhydramine 50 mg IV and an H2 antagonist (cimetidine 300 mg or ranitidine 50 mg IV) 30 to 60 minutes before; do not give with neutrophils below 1500/µL, and repeat only after neutrophils have recovered to above 1500 and platelets to above 100,000 [55].
- Pembrolizumab: liver enzymes, creatinine and thyroid function at baseline and periodically, with monitoring for immune-related adverse events (pneumonitis, colitis, hepatitis, endocrinopathies) [33].
- Olaparib: dose modifications: reduce to 250 mg and then 200 mg twice daily; CrCl 31 to 50: 200 mg twice daily; avoid strong/moderate CYP3A inhibitors (if unavoidable, 100 or 150 mg twice daily) [38]. Monitoring: complete blood count at baseline and monthly; evaluate for MDS/AML in prolonged cytopenia [38].
- Pertuzumab and trastuzumab: in taxane-containing regimens, infusion order: pertuzumab and trastuzumab (in either order), then the taxane; observe for 30 to 60 minutes after each pertuzumab infusion [34]. Missed dose: interval of less than 6 weeks: 420 mg pertuzumab and 6 mg/kg trastuzumab; 6 weeks or more: reload (840 mg and 8 mg/kg) [34]. Pertuzumab has no dose reductions and is stopped when trastuzumab is stopped [34]. Do not substitute trastuzumab, T-DM1 and T-DXd for one another [35, 37]. LVEF thresholds are given in the note of each regimen.
- Trastuzumab deruxtecan (T-DXd): the drug is highly emetogenic, and antiemetic prophylaxis is required. ILD: grade 1, withhold until complete resolution (same dose if it resolves within 28 days, otherwise reduce by one level); grade 2 or higher, discontinue permanently and give corticosteroids; ILD has been seen more often in moderate renal impairment, which calls for closer monitoring. Dose reduction: 4.4 and then 3.2 mg/kg. LVEF before starting and periodically; grade 4 neutropenia: withhold and reduce by one level [37].
- Ribociclib: ECG before starting, and start only if QTcF is below 450 ms; repeat around day 14 of the first cycle; liver tests and blood counts every 2 weeks for the first 2 cycles; do not use with tamoxifen (QT prolongation) [40].
- Abemaciclib: diarrhea: start antidiarrheal medication and fluids at the first loose stool; grade 3 or higher: withhold until grade 1, then resume at a lower dose; dose reduction: 100 mg and then 50 mg twice daily [39].
- Palbociclib: blood counts before starting, at the start of each cycle and on day 15 of the first two cycles; reduce to 100 mg and then 75 mg; with a strong CYP3A inhibitor, 75 mg [41].
- Fulvestrant: in moderate hepatic impairment (Child-Pugh B), 250 mg [42].
- Pre- or perimenopausal women: in regimens containing an aromatase inhibitor or fulvestrant with a CDK4/6 inhibitor or inavolisib, a GnRH/LHRH agonist is required [39, 40, 41, 42, 45].
For physicians
Early HER2-negative disease: chemotherapy, immunotherapy and adjuvant therapy
AC followed by paclitaxel (dose-dense every 2 weeks, or every 3 weeks)
High-risk early HER2-negative breast cancer (high-risk hormone receptor-positive or triple-negative), before or after surgery
High-risk early HER2-negative breast cancer (high-risk hormone receptor-positive or triple-negative), before or after surgery [4, 35]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Phase 1: 4 cycles | |||
| Doxorubicin | 60 mg/m² | IV | Day 1 |
| Cyclophosphamide | 600 mg/m² | IV | Day 1 |
| Phase 2: 12 weeks | |||
| Paclitaxel | 80 mg/m² (or 175 mg/m² every 3 weeks) | IV | Weekly, 12 doses |
Dose source: AC 60/600 mg/m² every 3 weeks for 4 cycles, followed by paclitaxel 80 mg/m² weekly or 175 mg/m² every 3 weeks for a total of 12 weeks (NSABP B-31 and NCCTG N9831) [35]; dose-dense ddAC 60/600 every 2 weeks for 4 cycles, then paclitaxel 80 weekly for 12 weeks (BERENICE cohort) [34].
Why dose-dense: in CALGB 9741, administration every 2 weeks with filgrastim improved disease-free survival (RR 0.74) and overall survival (RR 0.69), with less severe neutropenia [52]; the Pan-Asian ESMO guideline considers the dose-dense schedule with G-CSF an option [I, B] [54].
TC (docetaxel + cyclophosphamide)
Early HER2-negative breast cancer requiring adjuvant chemotherapy; an anthracycline-free alternativeCycle length: Every 21 days
Early HER2-negative breast cancer requiring adjuvant chemotherapy; an anthracycline-free alternative [51]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Docetaxel | 75 mg/m² | IV | Day 1 |
| Cyclophosphamide | 600 mg/m² | IV | Day 1 |
In US Oncology 9735, at 7-year follow-up, 4 cycles of TC gave better disease-free survival (81% vs 75%; HR 0.74) and overall survival (87% vs 82%; HR 0.69) than 4 cycles of AC (60/600 mg/m²); febrile neutropenia with TC was more frequent in older women [51].
Neoadjuvant pembrolizumab + chemotherapy, then adjuvant pembrolizumab (KEYNOTE-522)
High-risk early TNBC: tumor larger than 1 cm and up to 2 cm with nodal involvement, or larger than 2 cm regardless of nodal status; independent of PD-L1; no active autoimmune disease requiring systemic treatment in the past 2 yearsCycle length: Every 21 days
High-risk early TNBC: tumor larger than 1 cm and up to 2 cm with nodal involvement, or larger than 2 cm regardless of nodal status; independent of PD-L1; no active autoimmune disease requiring systemic treatment in the past 2 years [33]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Neoadjuvant, cycles 1–4 | |||
| Pembrolizumab | 200 mg (or 400 mg every 6 weeks) | IV, 30 min; before chemotherapy | Day 1 |
| Paclitaxel | 80 mg/m² | IV | Days 1, 8 and 15 |
| Carboplatin | AUC 5 (or AUC 1.5 weekly) | IV | Day 1 (or days 1, 8 and 15) |
| Neoadjuvant, cycles 5–8 | |||
| Pembrolizumab | 200 mg | IV | Day 1 |
| Doxorubicin or epirubicin | 60 mg/m² (epirubicin 90 mg/m²) | IV | Day 1 |
| Cyclophosphamide | 600 mg/m² | IV | Day 1 |
| Adjuvant, after surgery | |||
| Pembrolizumab | 200 mg (or 400 mg every 6 weeks) | IV | Day 1, 9 cycles |
If the disease progresses, or unacceptable pembrolizumab-related toxicity occurs, during the neoadjuvant phase, adjuvant pembrolizumab is not given [33].
Evidence: KEYNOTE-522 (2024), KEYNOTE-522 (2020)
Adjuvant capecitabine (CREATE-X)
HER2-negative breast cancer with residual invasive disease after neoadjuvant chemotherapy containing an anthracycline and/or a taxane; greatest benefit in triple-negative diseaseCycle length: Every 21 days
HER2-negative breast cancer with residual invasive disease after neoadjuvant chemotherapy containing an anthracycline and/or a taxane; greatest benefit in triple-negative disease [31]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Capecitabine | 1250 mg/m² twice daily | Oral | Days 1–14 |
CREATE-X dose and schedule from a published review of post-neoadjuvant trials [53]. Pan-Asian ESMO: for residual disease in patients who have not received an immune checkpoint inhibitor, 6 to 8 cycles of capecitabine [I, A]; the combination of olaparib and capecitabine in BRCA carriers is not recommended [I, E]; for residual disease after ICI-containing neoadjuvant therapy, concurrent ICI and capecitabine may be considered on an individual basis [V, C] [54].
Before starting: DPYD genetic testing (complete DPD deficiency carries a risk of fatal toxicity, and capecitabine should be avoided in these patients) [46]. Kidneys: reduce the dose by 25% for CrCl 30 to 50 mL/min; no dose has been established for CrCl below 30 [46]. With vitamin K antagonists (such as warfarin), the risk of bleeding increases (boxed warning) [46].
Evidence: CREATE-X (2017)
Adjuvant olaparib (OlympiA)
Germline BRCA1/2 mutation, HER2-negative, high risk, after completion of neoadjuvant or adjuvant chemotherapy and local treatmentCycle length: Continuous
Germline BRCA1/2 mutation, HER2-negative, high risk, after completion of neoadjuvant or adjuvant chemotherapy and local treatment [38, 54]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Olaparib | 300 mg twice daily | Oral | Continuous |
Start only after hematologic toxicity from prior chemotherapy has recovered to grade 1 or lower [38].
Evidence: OlympiA (2026), OlympiA (2021)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Early HER2-positive disease: before and after surgery
TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab)
Stage II–III HER2-positive breast cancer (IHC 3+ or ISH-positive), neoadjuvant (or adjuvant)Cycle length: Every 21 days
Stage II–III HER2-positive breast cancer (IHC 3+ or ISH-positive), neoadjuvant (or adjuvant) [34]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| 6 cycles | |||
| Docetaxel | 75 mg/m² (dose escalation is not recommended) | IV | Day 1 |
| Carboplatin | AUC 6 | IV | Day 1 |
| 6 cycles, then up to 1 year | |||
| Trastuzumab | Loading dose 8 mg/kg, then 6 mg/kg | IV (first infusion over 90 min, subsequent infusions over 30 to 90 min) | Day 1 |
| Pertuzumab | Loading dose 840 mg, then 420 mg | IV (first infusion over 60 min, subsequent infusions over 30 to 60 min) | Day 1 |
Heart: baseline LVEF of at least 55% in early disease; assess about every 12 weeks; if LVEF falls below 50% with a decrease of 10 points or more from baseline, withhold for at least 3 weeks [34].
Dose-dense AC followed by weekly paclitaxel + trastuzumab ± pertuzumab
Early HER2-positive breast cancer, neoadjuvant or adjuvant (anthracycline-containing regimen)
Early HER2-positive breast cancer, neoadjuvant or adjuvant (anthracycline-containing regimen) [34, 35]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Phase 1: 4 cycles | |||
| Doxorubicin + cyclophosphamide | 60 + 600 mg/m² | IV | Day 1, every 2 weeks with G-CSF (or every 3 weeks) |
| Phase 2: 12 weeks | |||
| Paclitaxel | 80 mg/m² | IV | Weekly |
| From the start of paclitaxel | |||
| Trastuzumab | 8 mg/kg, then 6 mg/kg every 3 weeks (or 4, then 2 mg/kg weekly with paclitaxel) | IV | Day 1 |
| Pertuzumab | 840 mg, then 420 mg every 3 weeks | IV | Day 1 |
Anti-HER2 drugs are started after the anthracycline has been completed; LVEF must be at least 50% before they are started [34]. Continuing trastuzumab beyond 1 year is not recommended [35]. Trastuzumab and the heart: for an absolute LVEF decrease of 16% or more, or an LVEF below normal with a decrease of 10% or more, withhold for at least 4 weeks; for a persistent decline lasting more than 8 weeks or more than 3 interruptions, discontinue permanently [35].
Stage I (T1a–b N0): Pan-Asian ESMO suggests upfront surgery followed by 12 weeks of paclitaxel with 1 year of trastuzumab [III, B] [54]; in this setting, trastuzumab is given at 4 mg/kg and then 2 mg/kg weekly for 12 weeks, and, one week after the last weekly dose, 6 mg/kg every 3 weeks to complete 52 weeks [35].
Adjuvant T-DM1 (KATHERINE)
HER2-positive with residual invasive disease after neoadjuvant therapy containing a taxane and trastuzumabCycle length: Every 21 days
HER2-positive with residual invasive disease after neoadjuvant therapy containing a taxane and trastuzumab [15, 36]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab emtansine (T-DM1) | 3.6 mg/kg (do not exceed this dose) | IV; first infusion over 90 min, subsequent infusions over 30 min | Day 1 |
Dose reduction: 3 and then 2.4 mg/kg; do not re-escalate after a reduction [36]. Monitoring: liver enzymes and bilirubin, platelets, LVEF; discontinue permanently for ILD/pneumonitis; for grade 3–4 neuropathy, withhold until grade 2 or lower [36]. Observe for 90 minutes after the first infusion and for 30 minutes after subsequent infusions [36].
Evidence: KATHERINE (2025), KATHERINE (2019)
Adjuvant T-DXd (DESTINY-Breast05)
High-risk HER2-positive with residual invasive disease after neoadjuvant therapyCycle length: Every 21 days
High-risk HER2-positive with residual invasive disease after neoadjuvant therapy [7, 37]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (T-DXd) | 5.4 mg/kg | IV (do not dilute with sodium chloride solution) | Day 1 |
ILD: in the adjuvant setting, rule out radiation pneumonitis [37].
Evidence: DESTINY-Breast05 (2026)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Early hormone receptor-positive disease: hormone therapy ± CDK4/6 inhibitor
Adjuvant hormone therapy
Early hormone receptor-positive breast cancerCycle length: Continuous
Early hormone receptor-positive breast cancer [4, 54]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pre- or postmenopausal | |||
| Tamoxifen | 20 mg once daily | Oral | Continuous |
| Postmenopausal (or with ovarian suppression) | |||
| Anastrozole | 1 mg once daily | Oral | Continuous |
| Letrozole | 2.5 mg once daily | Oral | Continuous |
| Exemestane | 25 mg once daily after a meal | Oral | Continuous |
Abemaciclib + hormone therapy (monarchE)
HR-positive/HER2-negative, node-positive, high risk: 4 or more involved lymph nodes, or 1 to 3 nodes with grade 3 or a tumor size of 5 cm or moreCycle length: Continuous
HR-positive/HER2-negative, node-positive, high risk: 4 or more involved lymph nodes, or 1 to 3 nodes with grade 3 or a tumor size of 5 cm or more [39]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Abemaciclib | 150 mg twice daily | Oral | Continuous |
| Tamoxifen or an aromatase inhibitor | Standard dose | Oral | Continuous |
Monitoring: blood counts and liver tests before starting, every 2 weeks for the first 2 months, monthly for the next 2 months and then as clinically indicated [39]. Venous thromboembolism: in early disease, discontinue for VTE of any grade [39]. Severe hepatic impairment: reduce the dosing frequency to once daily [39].
Evidence: monarchE (2026), monarchE (2020), monarchE (2024)
Ribociclib + nonsteroidal aromatase inhibitor (NATALEE)
HR-positive/HER2-negative stage IIB–III, or stage IIA with nodal involvement, or node-negative stage IIA with grade 3, or grade 2 with Ki-67 ≥20% or high genomic riskEach drug’s schedule in the table
HR-positive/HER2-negative stage IIB–III, or stage IIA with nodal involvement, or node-negative stage IIA with grade 3, or grade 2 with Ki-67 ≥20% or high genomic risk [40]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ribociclib | 400 mg once daily | Oral | Days 1–21, every 28 days |
| Letrozole or anastrozole (± goserelin) | 2.5 or 1 mg daily | Oral | Continuous |
Liver tests and blood counts: after the first 2 cycles, at the start of each of the next 4 cycles [40]. Dose reduction: 200 mg daily; below that, discontinue [40].
Evidence: NATALEE (2025), NATALEE (2024)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Advanced hormone receptor-positive / HER2-negative disease
Hormone therapy + CDK4/6 inhibitor (PALOMA-2, MONALEESA-2, MONARCH 3; after progression: PALOMA-3)
Advanced HR-positive/HER2-negative disease; first-line with an aromatase inhibitor, or with fulvestrant after prior hormone therapy
Advanced HR-positive/HER2-negative disease; first-line with an aromatase inhibitor, or with fulvestrant after prior hormone therapy [23, 24, 26, 30, 32]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| One of three drugs | |||
| Palbociclib | 125 mg once daily | Oral | Days 1–21 |
| Ribociclib | 600 mg once daily | Oral | Days 1–21 |
| Abemaciclib | 150 mg twice daily | Oral | Continuous |
| Combined with | |||
| Letrozole (or anastrozole 1 mg) | 2.5 mg once daily | Oral | Continuous |
| Or combined with | |||
| Fulvestrant | 500 mg (two 5-mL injections, one in each buttock) | IM, slowly | Days 1, 15 and 29, then monthly |
Ribociclib: reduce to 400 mg and then 200 mg [40]. Abemaciclib: monotherapy 200 mg twice daily [39].
Evidence: MONALEESA-2 (2022), MONARCH 3 (2017), PALOMA-2 (2016)
Exemestane + everolimus (BOLERO-2)
Postmenopausal women with advanced HR-positive/HER2-negative disease after failure of letrozole or anastrozoleCycle length: Continuous
Postmenopausal women with advanced HR-positive/HER2-negative disease after failure of letrozole or anastrozole [29, 43]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Everolimus | 10 mg once daily | Oral | Continuous |
| Exemestane | 25 mg once daily after a meal | Oral | Continuous |
From the first day, an alcohol-free dexamethasone mouthwash (swish and spit) to reduce stomatitis; avoid mouthwashes containing alcohol, hydrogen peroxide, iodine or thyme [43]. Monitor for noninfectious pneumonitis and infections; blood glucose and lipids, renal function and blood counts before starting and periodically [43].
Evidence: BOLERO-2 (2012)
Inavolisib + palbociclib + fulvestrant (INAVO120)
Advanced HR-positive/HER2-negative disease with a PIK3CA mutation (in a plasma sample), endocrine-resistant: recurrence during adjuvant hormone therapy or within 12 months of completing itEach drug’s schedule in the table
Advanced HR-positive/HER2-negative disease with a PIK3CA mutation (in a plasma sample), endocrine-resistant: recurrence during adjuvant hormone therapy or within 12 months of completing it [18, 45]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Inavolisib | 9 mg once daily | Oral | Continuous |
| Palbociclib | 125 mg once daily | Oral | Days 1–21, every 28 days |
| Fulvestrant | 500 mg | IM | Days 1, 15 and 29, then monthly |
Blood glucose: measure and optimize fasting glucose and HbA1c before starting, and monitor during treatment; fasting glucose above 160 to 250 mg/dL: withhold until 160 or lower [45]. Dose reduction: 6 and then 3 mg; lower starting dose in moderate and severe renal impairment [45].
Evidence: INAVO120 (2024)
Switch to camizestrant on emergence of an ESR1 mutation (SERENA-6; trial regimen)
Advanced ER-positive/HER2-negative disease after at least 6 months of first-line treatment with an aromatase inhibitor + CDK4/6 inhibitor, with an ESR1 mutation emerging in ctDNA (monitored every 2 to 3 months) without radiologic progressionCycle length: Continuous
Advanced ER-positive/HER2-negative disease after at least 6 months of first-line treatment with an aromatase inhibitor + CDK4/6 inhibitor, with an ESR1 mutation emerging in ctDNA (monitored every 2 to 3 months) without radiologic progression [19]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Camizestrant (in place of the aromatase inhibitor) | 75 mg once daily | Oral | Continuous |
| The same CDK4/6 inhibitor as before | Previous dose | Oral | Continued |
A new drug; dose from the SERENA-6 trial [19]. Treatment discontinuation due to adverse events was 1.3% [19].
Evidence: SERENA-6 (2025)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Advanced HER2-positive and HER2-low disease
THP (pertuzumab + trastuzumab + docetaxel; CLEOPATRA)
HER2-positive metastatic disease, first-line (no prior anti-HER2 therapy or chemotherapy for metastatic disease)Cycle length: Every 21 days
HER2-positive metastatic disease, first-line (no prior anti-HER2 therapy or chemotherapy for metastatic disease) [21, 34]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pertuzumab | Loading dose 840 mg, then 420 mg | IV | Day 1 |
| Trastuzumab | Loading dose 8 mg/kg, then 6 mg/kg | IV | Day 1 |
| At least 6 cycles | |||
| Docetaxel | 75 mg/m² (up to 100 mg/m² if tolerated) | IV | Day 1 |
Baseline LVEF of at least 50%, monitored about every 12 weeks; LVEF below 40%, or 40 to 45% with a decrease of 10 points or more: withhold for at least 3 weeks [34]. NCCN (version 4.2026) considers THP the preferred first-line approach for most patients [21].
Evidence: CLEOPATRA (2015), CLEOPATRA (2012)
T-DXd + pertuzumab (DESTINY-Breast09)
HER2-positive metastatic disease, first-lineCycle length: Every 21 days
HER2-positive metastatic disease, first-line [8, 37]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (T-DXd) | 5.4 mg/kg | IV | Day 1 |
| Pertuzumab | Cycle 1: 840 mg; then 420 mg | IV, 30 min after T-DXd | Day 1 |
Because of the risk of ILD and the absence of crossover, NCCN lists this combination among “other recommended options” [21].
Evidence: DESTINY-Breast09 (2026)
Single-agent T-DXd (DESTINY-Breast03, 04, 06)
HER2-positive after prior anti-HER2 therapy; HER2-low (IHC 1+ or 2+ with negative ISH) after prior chemotherapy; HR-positive HER2-low or HER2-ultralow (IHC 0 with membrane staining) after one or more lines of hormone therapyCycle length: Every 21 days
HER2-positive after prior anti-HER2 therapy [20]; HER2-low (IHC 1+ or 2+ with negative ISH) after prior chemotherapy [11]; HR-positive HER2-low or HER2-ultralow (IHC 0 with membrane staining) after one or more lines of hormone therapy [28, 37]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (T-DXd) | 5.4 mg/kg | IV | Day 1 |
Evidence: DESTINY-Breast03 (2024), DESTINY-Breast06 (2024), DESTINY-Breast04 (2022)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Advanced triple-negative disease or disease with a germline BRCA mutation
Pembrolizumab + chemotherapy (KEYNOTE-355)
Recurrent unresectable or metastatic TNBC with PD-L1 CPS ≥10 (22C3), no prior chemotherapy for metastatic diseaseEach drug’s schedule in the table
Recurrent unresectable or metastatic TNBC with PD-L1 CPS ≥10 (22C3), no prior chemotherapy for metastatic disease [25, 33]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg every 3 weeks (or 400 mg every 6 weeks) | IV, before chemotherapy | Day 1 |
| Chemotherapy: one of three | |||
| Paclitaxel | 90 mg/m² | IV | Days 1, 8 and 15 every 28 days |
| Nab-paclitaxel | 100 mg/m² | IV | Days 1, 8 and 15 every 28 days |
| Gemcitabine + carboplatin | 1000 mg/m² + AUC 2 | IV | Days 1 and 8 every 21 days |
With CPS between 1 and 10, the overall survival benefit was not significant [25].
Evidence: KEYNOTE-355 (2022)
Olaparib in metastatic disease (OlympiAD)
HER2-negative metastatic breast cancer with a germline BRCA1/2 mutationCycle length: Continuous
HER2-negative metastatic breast cancer with a germline BRCA1/2 mutation [27, 38]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Olaparib | 300 mg twice daily | Oral | Continuous |
Evidence: OlympiAD (2017)
Sacituzumab govitecan + pembrolizumab (ASCENT-04/KEYNOTE-D19)
Untreated advanced TNBC with PD-L1 CPS ≥10; if treated at an early stage, at least 6 months between the end of curative treatment and recurrenceCycle length: Every 21 days
Untreated advanced TNBC with PD-L1 CPS ≥10; if treated at an early stage, at least 6 months between the end of curative treatment and recurrence [33]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Sacituzumab govitecan | 10 mg/kg (do not exceed) | IV | Days 1 and 8 |
| Pembrolizumab | 200 mg | IV | Day 1 |
Premedication: an antipyretic and H1 and H2 antihistamines before the infusion (plus a corticosteroid if there is a history of infusion reactions); two- or three-drug antiemetic prophylaxis (dexamethasone with a 5-HT3 or NK1 antagonist) [44]. Neutropenia: primary G-CSF prophylaxis from the first cycle in patients at high risk of febrile neutropenia; give on day 1 with an ANC of at least 1500 and on day 8 with an ANC of at least 1000 [44]. UGT1A1*28 homozygotes are at higher risk of neutropenia and anemia [44]. Dose reduction: 7.5 and then 5 mg/kg [44]. Do not substitute with irinotecan-containing drugs [44].
Evidence: ASCENT-04/KEYNOTE-D19 (2026)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Scientific evidence
Key studies
24 itemsOverall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer
Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer
Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer
Sustained benefit of adjuvant olaparib in women with germline BRCA1- and BRCA2-associated high-risk HER2-negative early breast cancer: updated results from the OlympiA phase III trial
Overall survival with abemaciclib in early breast cancer
Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer
Palbociclib and Letrozole in Advanced Breast Cancer
MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer
Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer
Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation
Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial
Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer
Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer
Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival
Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer
Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer
Inavolisib-Based Therapy in PIK3CA -Mutated Advanced Breast Cancer
First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer
Pembrolizumab for Early Triple-Negative Breast Cancer
Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer
Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer
Clinical guidelines
3 itemsBreast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology
Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer
References
55 referencesShow all references, 32 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
- 2
- 3
- 4
- 5Twenty-Year Follow-up of a Randomized Study Comparing Breast-Conserving Surgery with Radical Mastectomy for Early Breast Cancer
- 6
- 7
- 8
- 9Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
- 10
- 11
- 12
- 13
- 14
- 15
- 16Pembrolizumab for Early Triple-Negative Breast Cancer
- 17Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer
- 18
- 19
- 20
- 21
- 22Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer
- 23
- 24
- 25
- 26
- 27
- 28
- 29
- 30
- 31Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy
- 32
- 33
- 34
- 35
- 36
- 37
- 38
- 39
- 40
- 41
- 42
- 43
- 44
- 45
- 46
- 47
- 48ARIMIDEX (anastrozole) tablets, for oral use: prescribing information
- 49FEMARA (letrozole) tablets, for oral use: prescribing information
- 50
- 51
- 52Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741
- 53
- 54
- 55Paclitaxel injection: prescribing information
This page is based on reputable scientific sources and was last updated on 21 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.