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Review Article| Volume 2, ISSUE 1, P47-61, May 2022

Neoadjuvant Chemotherapy for Nonmetastatic Breast Cancer

How Response Impacts Locoregional and Adjuvant Systemic Therapy Decision Making
Published:April 07, 2022DOI:https://doi.org/10.1016/j.yao.2022.01.004

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      References

        • King T.A.
        • Morrow M.
        Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy.
        Nat Rev Clin Oncol. 2015; 12: 335-343
        • Burstein H.J.
        • Curigliano G.
        • Loibl S.
        • et al.
        Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019.
        Ann Oncol. 2019; 30: 1541-1557
      1. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology (Breast Cancer) Version 5.2021, June 28, 2021. Version 4.2021 — April 28, 2021.
        (Available at:) (Accessed July 05, 2021)
        • Dubsky P.
        • Pinker K.
        • Cardoso F.
        • et al.
        Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox.
        Lancet Oncol. 2021; 22: e18-e28
        • Murphy B.L.
        • Day C.N.
        • Hoskin T.L.
        • et al.
        Neoadjuvant Chemotherapy Use in Breast Cancer is Greatest in Excellent Responders: Triple-Negative and HER2+ Subtypes.
        Ann Surg Oncol. 2018; 25: 2241-2248
        • Early Breast Cancer Trialists' Collaborative G.
        Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials.
        Lancet Oncol. 2018; 19: 27-39
        • Montagna G.
        • Mamtani A.
        • Knezevic A.
        • et al.
        Selecting node-positive patients for axillary downstaging with neoadjuvant chemotherapy.
        Ann Surg Oncol. 2020; 27: 4515-4522
        • Swisher S.K.
        • Vila J.
        • Tucker S.L.
        • et al.
        Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy.
        Ann Surg Oncol. 2016; 23: 749-756
        • Mamtani A.
        • Barrio A.V.
        • King T.A.
        • et al.
        How Often Does Neoadjuvant Chemotherapy Avoid Axillary Dissection in Patients With Histologically Confirmed Nodal Metastases? Results of a Prospective Study.
        Ann Surg Oncol. 2016; 23: 3467-3474
        • Martelli G.
        • Barretta F.
        • Miceli R.
        • et al.
        Sentinel Node Biopsy alone or with Axillary Dissection in Breast Cancer Patients after Primary Chemotherapy: Long-term Results of a Prospective Interventional Study.
        Ann Surg. 2020; https://doi.org/10.1097/SLA.0000000000004562
        • Piltin M.A.
        • Hoskin T.L.
        • Day C.N.
        • et al.
        Oncologic Outcomes of Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy for Node-Positive Breast Cancer.
        Ann Surg Oncol. 2020; 27: 4795-4801
        • Wong S.M.
        • Basik M.
        • Florianova L.
        • et al.
        Oncologic Safety of Sentinel Lymph Node Biopsy Alone After Neoadjuvant Chemotherapy for Breast Cancer.
        Ann Surg Oncol. 2021; 28: 2621-2629
        • Barrio A.V.
        • Montagna G.
        • Mamtani A.
        • et al.
        Nodal Recurrence in Patients With Node-Positive Breast Cancer Treated With Sentinel Node Biopsy Alone After Neoadjuvant Chemotherapy-A Rare Event.
        JAMA Oncol. 2021; 7: 1851-1855
      2. Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery.
        (Available at:) (Accessed July 05, 2021)
      3. Eliminating Surgery After Systemic Therapy in Treating Patients With HER2 Positive or Triple Negative Breast Cancer.
        (Available at:) (Accessed July 05, 2021)
        • Masuda N.
        • Lee S.J.
        • Ohtani S.
        • et al.
        Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy.
        N Engl J Med. 2017; 376: 2147-2159
        • von Minckwitz G.
        • Huang C.S.
        • Mano M.S.
        • et al.
        Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.
        N Engl J Med. 2019; 380: 617-628
        • Tutt A.N.J.
        • Garber J.E.
        • Kaufman B.
        • et al.
        Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer.
        N Engl J Med. 2021; 384: 2394-2405
        • Cortazar P.
        • Zhang L.
        • Untch M.
        • et al.
        Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.
        Lancet. 2014; 384: 164-172
        • Fisher B.
        • Brown A.
        • Mamounas E.
        • et al.
        Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18.
        J Clin Oncol. 1997; 15: 2483-2493
        • Golshan M.
        • Cirrincione C.T.
        • Sikov W.M.
        • et al.
        Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance).
        Ann Surg. 2015; 262 ([discussion: 438–9]): 434-439
        • Golshan M.
        • Cirrincione C.T.
        • Sikov W.M.
        • et al.
        Impact of neoadjuvant therapy on eligibility for and frequency of breast conservation in stage II-III HER2-positive breast cancer: surgical results of CALGB 40601 (Alliance).
        Breast Cancer Res Treat. 2016; 160: 297-304
        • Petruolo O.
        • Sevilimedu V.
        • Montagna G.
        • et al.
        How Often Does Modern Neoadjuvant Chemotherapy Downstage Patients to Breast-Conserving Surgery?.
        Ann Surg Oncol. 2021; 28: 287-294
        • Fisher B.
        • Bryant J.
        • Wolmark N.
        • et al.
        Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.
        J Clin Oncol. 1998; 16: 2672-2685
        • Rubio I.T.
        • Wyld L.
        • Cardoso F.
        • et al.
        Perspectives on preoperative systemic treatment and breast conservative surgery: One step forward or two steps back?.
        Breast. 2018; 41: 133-135
        • Charalampoudis P.
        • Karakatsanis A.
        Neoadjuvant chemotherapy for early breast cancer.
        Lancet Oncol. 2018; 19: e128
        • Krug D.
        • Loibl S.
        Neoadjuvant chemotherapy for early breast cancer.
        Lancet Oncol. 2018; 19: e129
        • Mamtani A.
        • Sevilimedu V.
        • Le T.
        • et al.
        Is Locoregional Recurrence Higher Among Patients Who Downstage to Breast Conservation After Neoadjuvant Chemotherapy?.
        Ann Surg Oncol. 2021; 28: S49-S50
        • Classe J.M.
        • Bordes V.
        • Campion L.
        • et al.
        Sentinel lymph node biopsy after neoadjuvant chemotherapy for advanced breast cancer: results of Ganglion Sentinelle et Chimiotherapie Neoadjuvante, a French prospective multicentric study.
        J Clin Oncol. 2009; 27: 726-732
        • Hunt K.K.
        • Yi M.
        • Mittendorf E.A.
        • et al.
        Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients.
        Ann Surg. 2009; 250: 558-566
        • Pilewskie M.
        • Morrow M.
        Axillary Nodal Management Following Neoadjuvant Chemotherapy: A Review.
        JAMA Oncol. 2017; 3: 549-555
        • Boileau J.F.
        • Poirier B.
        • Basik M.
        • et al.
        Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study.
        J Clin Oncol. 2015; 33: 258-264
        • Boughey J.C.
        • Suman V.J.
        • Mittendorf E.A.
        • et al.
        Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial.
        JAMA. 2013; 310: 1455-1461
        • Classe J.M.
        • Loaec C.
        • Gimbergues P.
        • et al.
        Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study.
        Breast Cancer Res Treat. 2019; 173: 343-352
        • Kuehn T.
        • Bauerfeind I.
        • Fehm T.
        • et al.
        Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study.
        Lancet Oncol. 2013; 14: 609-618
        • Boughey J.C.
        • Suman V.J.
        • Mittendorf E.A.
        • et al.
        Factors affecting sentinel lymph node identification rate after neoadjuvant chemotherapy for breast cancer patients enrolled in ACOSOG Z1071 (Alliance).
        Ann Surg. 2015; 261: 547-552
        • Burstein H.J.
        • Curigliano G.
        • Thurlimann B.
        • et al.
        CUSTOMIZING LOCAL AND SYSTEMIC THERAPIES FOR WOMEN WITH EARLY BREAST CANCER: The St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.
        Ann Oncol. 2021; 32: 1216-1235
        • Cardoso F.
        • Kyriakides S.
        • Ohno S.
        • et al.
        Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2019; 30: 1674
        • Moo T.A.
        • Edelweiss M.
        • Hajiyeva S.
        • et al.
        Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?.
        Ann Surg Oncol. 2018; 25: 1488-1494
        • Moo T.A.
        • Pawloski K.R.
        • Flynn J.
        • et al.
        Is residual nodal disease at axillary dissection associated with tumor subtype in patients with low volume sentinel node metastasis after neoadjuvant chemotherapy?.
        Ann Surg Oncol. 2021; 28: 6044-6050
        • Wong S.M.
        • Almana N.
        • Choi J.
        • et al.
        Prognostic Significance of Residual Axillary Nodal Micrometastases and Isolated Tumor Cells After Neoadjuvant Chemotherapy for Breast Cancer.
        Ann Surg Oncol. 2019; 26: 3502-3509
        • Barron A.U.
        • Hoskin T.L.
        • Boughey J.C.
        Predicting non-sentinel lymph node metastases in patients with a positive sentinel lymph node after neoadjuvant chemotherapy.
        Ann Surg Oncol. 2018; 25: 2867-2874
        • Nguyen T.T.
        • Hoskin T.L.
        • Day C.N.
        • et al.
        Decreasing use of axillary dissection in node-positive breast cancer patients treated with neoadjuvant chemotherapy.
        Ann Surg Oncol. 2018; 25: 2596-2602
        • Di Micco R.
        • Zuber V.
        • Fiacco E.
        • et al.
        Sentinel node biopsy after primary systemic therapy in node positive breast cancer patients: Time trend, imaging staging power and nodal downstaging according to molecular subtype.
        Eur J Surg Oncol. 2019; 45: 969-975
        • Kahler-Ribeiro-Fontana S.
        • Pagan E.
        • Magnoni F.
        • et al.
        Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up.
        Eur J Surg Oncol. 2021; 47: 804-812
        • Giuliano A.E.
        • Ballman K.
        • McCall L.
        • et al.
        Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial.
        Ann Surg. 2016; 264: 413-420
        • Metzger-Filho O.
        • Sun Z.
        • Viale G.
        • et al.
        Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX.
        J Clin Oncol. 2013; 31: 3083-3090
        • Pagani O.
        • Price K.N.
        • Gelber R.D.
        • et al.
        Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century.
        Breast Cancer Res Treat. 2009; 117: 319-324
        • Piccart M.
        • Procter M.
        • Fumagalli D.
        • et al.
        Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up.
        J Clin Oncol. 2021; 39: 1448-1457
        • Houssami N.
        • Macaskill P.
        • von Minckwitz G.
        • et al.
        Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy.
        Eur J Cancer. 2012; 48: 3342-3354
        • Haque W.
        • Verma V.
        • Hatch S.
        • et al.
        Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy.
        Breast Cancer Res Treat. 2018; 170: 559-567
        • Goorts B.
        • van Nijnatten T.J.
        • de Munck L.
        • et al.
        Clinical tumor stage is the most important predictor of pathological complete response rate after neoadjuvant chemotherapy in breast cancer patients.
        Breast Cancer Res Treat. 2017; 163: 83-91
        • Gianni L.
        • Pienkowski T.
        • Im Y.H.
        • et al.
        Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial.
        Lancet Oncol. 2012; 13: 25-32
        • von Minckwitz G.
        • Schneeweiss A.
        • Loibl S.
        • et al.
        Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial.
        Lancet Oncol. 2014; 15: 747-756
        • Nanda R.
        • Liu M.C.
        • Yau C.
        • et al.
        Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial.
        JAMA Oncol. 2020; 6: 676-684
        • Kuerer H.M.
        • Vrancken Peeters M.
        • Rea D.W.
        • et al.
        Nonoperative Management for Invasive Breast Cancer After Neoadjuvant Systemic Therapy: Conceptual Basis and Fundamental International Feasibility Clinical Trials.
        Ann Surg Oncol. 2017; 24: 2855-2862
        • Heil J.
        • Pfob A.
        • Morrow M.
        De-escalation of breast and axillary surgery in exceptional responders to neoadjuvant systemic treatment.
        Lancet Oncol. 2021; 22: 435-436
        • Daveau C.
        • Savignoni A.
        • Abrous-Anane S.
        • et al.
        Is radiotherapy an option for early breast cancers with complete clinical response after neoadjuvant chemotherapy?.
        Int J Radiat Oncol Biol Phys. 2011; 79: 1452-1459
        • van la Parra R.F.
        • Kuerer H.M.
        Selective elimination of breast cancer surgery in exceptional responders: historical perspective and current trials.
        Breast Cancer Res. 2016; 18: 28
        • Fowler A.M.
        • Mankoff D.A.
        • Joe B.N.
        Imaging Neoadjuvant Therapy Response in Breast Cancer.
        Radiology. 2017; 285: 358-375
        • Li H.
        • Yao L.
        • Jin P.
        • et al.
        MRI and PET/CT for evaluation of the pathological response to neoadjuvant chemotherapy in breast cancer: A systematic review and meta-analysis.
        Breast. 2018; 40: 106-115
        • Rauch G.M.
        • Adrada B.E.
        • Kuerer H.M.
        • et al.
        Multimodality Imaging for Evaluating Response to Neoadjuvant Chemotherapy in Breast Cancer.
        AJR Am J Roentgenol. 2017; 208: 290-299
        • Weber J.J.
        • Jochelson M.S.
        • Eaton A.
        • et al.
        MRI and Prediction of Pathologic Complete Response in the Breast and Axilla after Neoadjuvant Chemotherapy for Breast Cancer.
        J Am Coll Surg. 2017; 225: 740-746
        • van Loevezijn A.A.
        • van der Noordaa M.E.M.
        • van Werkhoven E.D.
        • et al.
        Minimally Invasive Complete Response Assessment of the Breast After Neoadjuvant Systemic Therapy for Early Breast Cancer (MICRA trial): Interim Analysis of a Multicenter Observational Cohort Study.
        Ann Surg Oncol. 2021; 28: 3243-3253
        • Heil J.
        • Pfob A.
        • Sinn H.P.
        • et al.
        Diagnosing Pathologic Complete Response in the Breast After Neoadjuvant Systemic Treatment of Breast Cancer Patients by Minimal Invasive Biopsy: Oral Presentation at the San Antonio Breast Cancer Symposium on Friday, December 13, 2019, Program Number GS5-03.
        Ann Surg. 2022; 275: 576-581
      4. Abstract GS5-05: Primary analysis of NRG-BR005, a phase II trial assessing accuracy of tumor bed biopsies in predicting pathologic complete response (pCR) in patients with clinical/radiological complete response after neoadjuvant chemotherapy (NCT) to explore the feasibility of breast-conserving treatment without surgery.
        (Available at:) (Accessed July 10, 2021)
        • Tasoulis M.K.
        • Lee H.B.
        • Yang W.
        • et al.
        Accuracy of Post-Neoadjuvant Chemotherapy Image-Guided Breast Biopsy to Predict Residual Cancer.
        JAMA Surg. 2020; 155: e204103
        • Mamounas E.P.
        • Anderson S.J.
        • Dignam J.J.
        • et al.
        Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27.
        J Clin Oncol. 2012; 30: 3960-3966
        • Henke G.
        • Knauer M.
        • Ribi K.
        • et al.
        Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-III trial.
        Trials. 2018; 19: 667
        • Carey L.A.
        • Metzger R.
        • Dees E.C.
        • et al.
        American Joint Committee on Cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome.
        J Natl Cancer Inst. 2005; 97: 1137-1142
        • Liedtke C.
        • Mazouni C.
        • Hess K.R.
        • et al.
        Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer.
        J Clin Oncol. 2008; 26: 1275-1281
        • Symmans W.F.
        • Wei C.
        • Gould R.
        • et al.
        Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype.
        J Clin Oncol. 2017; 35: 1049-1060
        • File D.
        • Curigliano G.
        • Carey L.A.
        Escalating and De-escalating Therapy for Early-Stage HER2-Positive Breast Cancer.
        Am Soc Clin Oncol Educ Book. 2020; 40: 1-11
        • Leon-Ferre R.A.
        • Hieken T.J.
        • Boughey J.C.
        The Landmark Series: Neoadjuvant Chemotherapy for Triple-Negative and HER2-Positive Breast Cancer.
        Ann Surg Oncol. 2021; 28: 2111-2119
        • Gianni L.
        • Eiermann W.
        • Semiglazov V.
        • et al.
        Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort.
        Lancet. 2010; 375: 377-384
        • Gianni L.
        • Pienkowski T.
        • Im Y.H.
        • et al.
        5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial.
        Lancet Oncol. 2016; 17: 791-800
        • Schneeweiss A.
        • Chia S.
        • Hickish T.
        • et al.
        Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).
        Ann Oncol. 2013; 24: 2278-2284
        • Robidoux A.
        • Tang G.
        • Rastogi P.
        • et al.
        Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial.
        Lancet Oncol. 2013; 14: 1183-1192
        • Carey L.A.
        • Berry D.A.
        • Cirrincione C.T.
        • et al.
        Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib.
        J Clin Oncol. 2016; 34: 542-549
        • de Azambuja E.
        • Holmes A.P.
        • Piccart-Gebhart M.
        • et al.
        Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response.
        Lancet Oncol. 2014; 15: 1137-1146
        • von Minckwitz G.
        • Procter M.
        • de Azambuja E.
        • et al.
        Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.
        N Engl J Med. 2017; 377: 122-131
      5. CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy.
        (Available at:) (Accessed July 05, 2021)
        • Early Breast Cancer Trialists' Collaborative G.
        Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials.
        Lancet. 2019; 393: 1440-1452
        • Petrelli F.
        • Coinu A.
        • Lonati V.
        • et al.
        Neoadjuvant dose-dense chemotherapy for locally advanced breast cancer: a meta-analysis of published studies.
        Anticancer Drugs. 2016; 27: 702-708
        • Tutt A.
        • Tovey H.
        • Cheang M.C.U.
        • et al.
        Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.
        Nat Med. 2018; 24: 628-637
        • Sikov W.M.
        • Berry D.A.
        • Perou C.M.
        • et al.
        Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance).
        J Clin Oncol. 2015; 33: 13-21
        • Loibl S.
        • O'Shaughnessy J.
        • Untch M.
        • et al.
        Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial.
        Lancet Oncol. 2018; 19: 497-509
        • Schmid P.
        • Adams S.
        • Rugo H.S.
        • et al.
        Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.
        N Engl J Med. 2018; 379: 2108-2121
        • Schmid P.
        • Cortes J.
        • Pusztai L.
        • et al.
        Pembrolizumab for Early Triple-Negative Breast Cancer.
        N Engl J Med. 2020; 382: 810-821
        • Loibl S.
        • Untch M.
        • Burchardi N.
        • et al.
        A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study.
        Ann Oncol. 2019; 30: 1279-1288
      6. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study. 2019.
        (Available at:) (Accessed July 05, 2021)
        • Mittendorf E.A.
        • Zhang H.
        • Barrios C.H.
        • et al.
        Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial.
        Lancet. 2020; 396: 1090-1100
        • Schmid P.
        • Cortes J.
        • Dent R.
        • et al.
        VP7-2021: KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab D chemotherapy vs. placebo D chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early- stage TNBC.
        Ann Oncol. 2019; 30: v851-v934
        • Robson M.
        • Goessl C.
        • Domchek S.
        Olaparib for Metastatic Germline BRCA-Mutated Breast Cancer.
        N Engl J Med. 2017; 377: 1792-1793
        • Litton J.K.
        • Rugo H.S.
        • Ettl J.
        • et al.
        Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.
        N Engl J Med. 2018; 379: 753-763
      7. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. J Clin Oncol 2021.
        (Available at:) (Accessed July 09, 2021)
        • Sparano J.A.
        • Gray R.J.
        • Ravdin P.M.
        • et al.
        Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.
        N Engl J Med. 2019; 380: 2395-2405
        • Piccart M.
        • van 't Veer L.J.
        • Poncet C.
        • et al.
        70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age.
        Lancet Oncol. 2021; 22: 476-488
        • Piccart M.J.
        • Kalinsky K.
        • Gray R.
        • et al.
        Gene expression signatures for tailoring adjuvant chemotherapy of luminal breast cancer: stronger evidence, greater trust.
        Ann Oncol. 2021; 32: 1077-1082
        • Spring L.M.
        • Gupta A.
        • Reynolds K.L.
        • et al.
        Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis.
        JAMA Oncol. 2016; 2: 1477-1486
        • Montagna G.
        • Sevilimedu V.
        • Fornier M.
        • et al.
        How Effective is Neoadjuvant Endocrine Therapy (NET) in Downstaging the Axilla and Achieving Breast-Conserving Surgery?.
        Ann Surg Oncol. 2020; 27: 4702-4710
        • Kalinsky K.
        • Barlow W.
        • Meric-Bernstam F.
        • et al.
        Abstract GS3-00: First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder).
        Cancer Res. 2021; : 81
      8. A Study of the Use of Sentinel Lymph Node Biopsy in Women With Early-Stage, Palpable Node-Positive HR+/HER2- Breast Cancer Having Breast Conservation Therapy.
        (Available at:) (Accessed July 22, 2019)
        • Sinn B.V.
        • Loibl S.
        • Hanusch C.A.
        • et al.
        Immune-related Gene Expression Predicts Response to Neoadjuvant Chemotherapy but not Additional Benefit from PD-L1 Inhibition in Women with Early Triple-negative Breast Cancer.
        Clin Cancer Res. 2021; 27: 2584-2591
        • Radovich M.
        • Jiang G.
        • Hancock B.A.
        • et al.
        Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial.
        JAMA Oncol. 2020; 6: 1410-1415
      9. Assessing the Accuracy of Tumor Biopsies After Chemotherapy to Determine if Patients Can Avoid Breast Surgery.
        (Available at:) (Accessed July 10, 2021)
        • Hahnen E.
        • Lederer B.
        • Hauke J.
        • et al.
        Germline Mutation Status, Pathological Complete Response, and Disease-Free Survival in Triple-Negative Breast Cancer: Secondary Analysis of the GeparSixto Randomized Clinical Trial.
        JAMA Oncol. 2017; 3: 1378-1385