Indications for Neoadjuvant Chemotherapy (NAC) in Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Neoadjuvant chemotherapy (NAC):
    • Is appropriate for many patients with locally advanced breast cancer regardless of subtype:
      • Because a response may allow both less extensive surgery and improved surgical outcomes
    • Locally advanced disease is defined as:
      • Stage III cancers
      • As well as the subset of IIB cancers with T3 disease
    • In addition, patients with earlier stage, HER2+ disease (stage I or II) may also be candidates for neoadjuvant therapy, if one or more of the following criteria apply:
    • The patient desires breast-conserving surgery (BCS) but is not a candidate for BCS or is likely to have a suboptimal cosmetic outcome with BCS due to tumor location or size relative to the size of the patient’s breast, and may be a better candidate if neoadjuvant therapy decreases the extent of her tumor
    • The patient has limited axillary nodal involvement (N1), for which axillary lymph node dissection would be standard surgical management, but could be a candidate for sentinel lymph node sampling alone if converted to node-negative disease with neoadjuvant therapy
    • Surgery must be postponed awaiting consultation with plastic surgery regarding breast reconstruction, results of genetic testing, or resolution of an intercurrent illness, including pregnancy, and the patient and treating clinicians do not wish to delay initiation of treatment
    • Postoperative treatment with ado-trastuzumab emtansine (T-DM1) would be considered if the patient were found to have residual invasive disease in the breast or axillary nodes following NAC with single or dual HER2-targeted therapy
  • Pertuzumab:
    • Is a monoclonal antibody that binds to a different epitope on HER2 than trastuzumab:
      • Blocking the formation of HER2:HER3 heterodimers:
        • Which is believed to be an important mechanism of resistance to trastuzumab
    • While single-agent pertuzumab has demonstrated antitumor activity in patients with HER2-positive metastatic disease who progressed on trastuzumab:
      • It is typically given in combination with trastuzumab to maintain suppression of signaling initiated by HER2 homodimers
    • In 2013, the FDA granted accelerated approval for the addition of pertuzumab to NACT and trastuzumab:
      • For patients with HER2+ locally advanced, inflammatory, or early-stage (either greater than 2 cm in diameter or node positive) breast cancer
    • We routinely add pertuzumab in patients receiving NACT and trastuzumab:
      • Given evidence that pertuzumab enhances locoregional responses:
        • Even though it increases the incidence and severity of treatment-related diarrhea as well as modestly increasing the frequency of hematologic toxicities
  • NeoSphere trial:
    • In the phase II NeoSphere trial:
      • 417 HER2+ patients received 12 weeks of neoadjuvant therapy composed of either 4 cycles of single-agent docetaxel with trastuzumab, pertuzumab, or both, or the combination of trastuzumab and pertuzumab without concurrent docetaxel
      • After surgery, all patients received anthracycline-based adjuvant chemotherapy (those randomized to trastuzumab and pertuzumab alone also received adjuvant docetaxel) and completed a year of treatment with trastuzumab
      • Those randomly assigned to docetaxel with pertuzumab and trastuzumab had a higher pathologic complete response (pCR) rate (46%):
        • Compared with those receiving docetaxel with just trastuzumab (29%) or just pertuzumab (24%)
      • Patients receiving pertuzumab and trastuzumab without docetaxel:
        • Had a pCR rate of 17%
  • References
    • Hayes DF. HER2 and breast cancer — a phenomenal success story. N Engl J Med. 2019;381(13):1284-1286.
    • Gianni L, Pienkowski T, Im Y-H, Tseng LM, Liu MC, Lluch A, 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(6):791-800.

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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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