Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Mini Oral session 3

1MO - Prognostic and biologic significance of HER2-low expression in early breast cancer


05 May 2022


Mini Oral session 3


Tumour Site

Breast Cancer


Paolo Tarantino


Annals of Oncology (2022) 33 (suppl_3): S123-S147. 10.1016/annonc/annonc888


P. Tarantino1, Q. Jin2, N. Tayob2, R. Jeselsohn1, S.J. Schnitt3, J. Vincuilla2, T. Parker2, S. Tyekucheva2, N.U. Lin4, M. Hughes1, A.C. Weiss2, T.A. King3, E.A. Mittendorf3, G. Curigliano5, S.M. Tolaney1

Author affiliations

  • 1 Dana Farber Cancer Institute, Boston/US
  • 2 Dana-Farber Cancer Institute, Boston/US
  • 3 Brigham and Women's Hospital, Boston/US
  • 4 Medical Oncology Department, Dana Farber Cancer Institute, 02215 - Boston/US
  • 5 IEO - Istituto Europeo di Oncologia, Milan/IT


Login to access the resources on OncologyPRO.

Abstract 1MO


Approximately 50% of HER2-negative breast cancers (BC) show HER2-low expression. It is unclear however whether HER2-low BC should be considered an individual biologic entity, prognostically distinct from HER2-zero BC.


Data were collected from an institutional database including all consecutive patients with BC who underwent surgery at Dana-Farber Brigham Cancer Center from 1/2016 to 3/2021. Tumors were defined as HER2-low if they had a HER2 IHC score of 1+ or 2+ with negative FISH, and HER2-zero if they had a HER2 IHC score of 0. Clinicopathologic characteristics and disease outcomes were compared between the two cohorts.


5235 HER2-negative BC patients were eligible for analysis; 4429 estrogen receptor (ER)+, 67 ER-low (1-9%), 739 ER-negative. Hormone receptor(HR)-expression was significantly more common among HER2-low compared with HER2-zero BC (89.9% vs 80.9%, p<0.001). Most other clinicopathological differences were explained by the different rate of HR+ tumors. When evaluated as a continuous variable, ER expression was significantly associated with HER2 expression (p<0.001), and the rate of HER2-low tumors increased progressively with increasing ER expression (Table). Among patients receiving neoadjuvant chemotherapy (n=657), those with HER2-zero tumors had higher pCR rates compared with HER2-low (27% vs 17%, p=0.002). However, statistical difference was lost when separately analyzing HR+ (8% vs 14%, p=0.078), ER-low (25% vs 38.9%, p=0.46), HR+ without ER-low (6.9% vs 10.4%, p=0.277), TNBC (30.8% vs 35.4%, p=0.40) and when adjusting for confounders. No difference in disease-free survival or overall survival was observed among patients with HR+ tumors or TNBC depending on HER2-low expression. Table: 1MO

Proportion of tumors with HER2-low versus HER2-zero expression according to tumor subtype and ER expression

TNBC ER-low (1-9%) ER-moderate (10-49%) ER-high (50-95%) ER-very-high (>95%)
HER2-low 40% 46% 55% 58% 62%
HER2-zero 60% 54% 45% 42% 38%


Our results do not support the interpretation of HER2-low BC as a distinct biologic subtype. HER2-low expression is continuously associated with the level of ER expression. ER-low tumors are enriched among HER2-zero cases and may confound prognostic analyses.

Legal entity responsible for the study

The authors.


Has not received any funding.


P. Tarantino: Financial Interests, Personal, Advisory Role: AstraZeneca. N.U. Lin: Financial Interests, Institutional, Other: Genentech, Merck, Pfizer; Financial Interests, Personal, Other: Seattle Genetics; Financial Interests, Personal, Advisory Role: Puma, Daiichi Sankyo, AstraZeneca, Denali Therapeutics, California Institute for Regenerative Medicine, Prelude Therapeutics. T.A. King: Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Personal, Advisory Role: PrecisCA Cancer Information Service. E.A. Mittendorf: Financial Interests, Personal, Advisory Role: Exact Science, Bristol Myers Squib, Genentech/Roche, Lilly, Merck. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly, Pfizer, Novartis, Merck, Gilead, Genentech/Roche, Eisai, Sanofi, Seagen, Daiichi Sankyo, 4D Pharma, Puma; Financial Interests, Personal, Other, Consultant: Nektar, NanoString, Athenex, Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, OncoPep, OncoSec, Certara, Mersana Therapeutics, Ellipses Pharma, G1 Therapeutics; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Invited Speaker, Invited Speaker for Pharma Supported Educational Activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks, Zentalis, Reveal Genomics, OncXerna; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Invited Speaker: CytomX. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.