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Adjuvant chemotherapy in patients with ER-negative/HER2-negative, T1abN0 breast cancer: a nationwide study

  • Epidemiology
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The purpose of this study was to examine the effect of chemotherapy on invasive disease-free survival (iDFS) and overall survival (OS) in a nationwide cohort of patients with estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative, T1abN0 breast cancer.


Patients with ER-negative/HER2-negative, T1abN0 breast cancer registered in the Danish Breast Cancer Group database between 2007 and 2016 were identified. The effect of adjuvant chemotherapy on iDFS and OS was analyzed with Cox proportional hazards analysis.


In total, 296 patients were included in the statistical analyses. Of these, 235 (79.4%) received chemotherapy and 61 patients (20.6%) did not. Patients treated with chemotherapy were significantly younger, had a significantly higher proportion of grade 3 tumors, T1b tumors, and tumors of ductal subtype. With 7.7 years of median follow-up, treatment with chemotherapy was associated with a significant improvement in OS in the adjusted analysis, Hazard Ratio 0.35 (95% Confidence Interval (0.15–0.81), p = 0.02), chemotherapy vs. no chemotherapy. In the unadjusted analyses, patients with both T1a and T1b tumors had significantly improved OS with chemotherapy. At 5 years, OS was 100% vs. 94.4% and 93.8% vs. 81.3% for patients with T1a and T1b tumors, respectively, chemotherapy vs. no chemotherapy. With 4.9 years of median follow-up, iDFS was not significantly improved with chemotherapy.


Patients with ER-negative/HER2-negative, T1abN0 breast cancer had significantly improved OS when treated with chemotherapy. This improvement was significant in patients with both T1a and T1b tumors, respectively. The effect was, however, limited in patients with T1a tumors.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to Danish legislation. Access to data from the Danish Breast Cancer Group database can be applied through Danish Clinical Registries (RKKP).


  1. Lynge E, Bak M, von Euler-Chelpin M, Kroman N, Lernevall A, Mogensen NB et al (2017) Outcome of breast cancer screening in Denmark. BMC Cancer 17(1):897

    Article  Google Scholar 

  2. The Danish Breast Cancer Group. Kvalitetsindikatorrapport for brystkræft 2021 [Internet]. [cited 2022 Aug 16]. Available from:årsrapport_2021_Publiceret_FINAL.pdf

  3. Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L (2016) Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol 13(11):674–690

    Article  CAS  Google Scholar 

  4. Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J et al (2011) Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin cancer Res an Off J Am Assoc Cancer Res 17(5):1082–1089

    Article  CAS  Google Scholar 

  5. Kwon JH, Kim YJ, Lee K-W, Oh D-Y, Park SY, Kim JH et al (2010) Triple negativity and young age as prognostic factors in lymph node-negative invasive ductal carcinoma of 1 cm or less. BMC Cancer 10:557

    Article  Google Scholar 

  6. Theriault RL, Litton JK, Mittendorf EA, Chen H, Meric-Bernstam F, Chavez-MacGregor M et al (2011) Age and survival estimates in patients who have node-negative T1ab breast cancer by breast cancer subtype. Clin Breast Cancer 11(5):325–331.

    Article  Google Scholar 

  7. Carey LA (2017) De-escalating and escalating systemic therapy in triple negative breast cancer. Breast 34(Suppl 1):S112–S115

    Article  Google Scholar 

  8. Ho AY, Gupta G, King TA, Perez CA, Patil SM, Rogers KH et al (2012) Favorable prognosis in patients with T1a/T1bN0 triple-negative breast cancers treated with multimodality therapy. Cancer 118(20):4944–4952

    Article  Google Scholar 

  9. Ren YX, Hao S, Jin X, Ye FG, Gong Y, Jiang YZ et al (2019) Effects of adjuvant chemotherapy in T1N0M0 triple-negative breast cancer. Breast 43:97–104.

    Article  Google Scholar 

  10. de Nonneville A, Gonçalves A, Zemmour C, Cohen M, Classe JM, Reyal F et al (2017) Adjuvant chemotherapy in pT1ab node-negative triple-negative breast carcinomas: results of a national multi-institutional retrospective study. Eur J Cancer 84:34–43

    Article  Google Scholar 

  11. An X, Lei X, Huang R, Luo R, Li H, Xu F et al (2020) Adjuvant chemotherapy for small, lymph node-negative, triple-negative breast cancer: a single-center study and a meta-analysis of the published literature. Cancer 126(Suppl 16):3837–3846

    Article  CAS  Google Scholar 

  12. Steenbruggen TG, van Werkhoven E, van Ramshorst MS, Dezentjé VO, Kok M, Linn SC et al (2020) Adjuvant chemotherapy in small node-negative triple-negative breast cancer. Eur J Cancer 135:66–74

    Article  CAS  Google Scholar 

  13. Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT et al (2019) Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 30(8):1194–1220

    Article  CAS  Google Scholar 

  14. National Comprehensive Cancer Network Clinical Practice Guidelines Oncology [Internet]. 2022 [cited 2022 Aug 15]. Available from:

  15. Burstein HJ, Curigliano G, Thürlimann B, Weber WP, Poortmans P, Regan MM et al (2021) 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 32(10):1216–1235

    Article  CAS  Google Scholar 

  16. Jensen M-B, Laenkholm A-V, Offersen BV, Christiansen P, Kroman N, Mouridsen HT et al (2018) The clinical database and implementation of treatment guidelines by the Danish Breast Cancer Cooperative Group in 2007–2016. Acta Oncol 57(1):13–18.

    Article  Google Scholar 

  17. Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JAW et al (2007) Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 25(15):2127–2132

    Article  Google Scholar 

  18. Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL et al (2020) Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol Off J Am Soc Clin Oncol 38(12):1346–1366

    Article  Google Scholar 

  19. Wolff AC, Hammond MEH, Schwartz JN, Hagerty KL, Allred DC, Cote RJ et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 25(1):118–145

    Article  CAS  Google Scholar 

  20. Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, Allison KH et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol Off J Am Soc Clin Oncol 31(31):3997–4013

    Article  Google Scholar 

  21. Danish Breast Cancer Group. Patologiprocedurer og molekylærpatologiske analyser ved brystkræft [Internet]. 2021 [cited 2022 Feb 1]. Available from:

  22. Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–410

    Article  CAS  Google Scholar 

  23. Danish Breast Cancer Group. Medicinsk behandling [Internet]. 2019 [cited 2022 Feb 21]. Available from:

  24. Gonzalez-Angulo AM, Litton JK, Broglio KR, Meric-Bernstam F, Rakkhit R, Cardoso F et al (2009) High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. J Clin Oncol 27(34):5700–5706

    Article  Google Scholar 

  25. Vaz-Luis I, Ottesen RA, Hughes ME, Mamet R, Burstein HJ, Edge SB et al (2014) Outcomes by tumor subtype and treatment pattern in women with small, node-negative breast cancer: a multi-institutional study. J Clin Oncol 32(20):2142–2150

    Article  Google Scholar 

  26. Olszewski AJ, Migdady Y, Boolbol SK, Klein P, Boachie-Adjei K, Sakr BJ et al (2013) Effects of adjuvant chemotherapy in HER2-positive or triple-negative pT1ab breast cancers: a multi-institutional retrospective study. Breast Cancer Res Treat 138(1):215–223

    Article  CAS  Google Scholar 

  27. Colonna SV, Higgins AK, Alvarez J, Saville BR, Lawrence J, Abramson VG (2016) Analysis of risk of recurrence by subtype in </= 1-cm breast tumors. Clin Breast Cancer 16(3):223–231

    Article  Google Scholar 

  28. Danish Breast Cancer Group. Systemisk behandling af brystkræft - II [Internet]. 2021 [cited 2022 Feb 2]. Available from:

  29. Stovgaard ES, Nielsen D, Hogdall E, Balslev E (2018) Triple negative breast cancer - prognostic role of immune-related factors: a systematic review. Acta Oncol 57(1):74–82

    Article  CAS  Google Scholar 

  30. Loi S, Drubay D, Adams S, Pruneri G, Francis PA, Lacroix-Triki M et al (2019) Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol 37(7):559–569.

    Article  Google Scholar 

  31. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E et al (2022) Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 387(1):9–20

    Article  CAS  Google Scholar 

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This study is part of a PhD-project supported by the Danish Cancer Society, Denmark (R246-A14574-19-S73); Interne Forskningsmidler, Herlev and Gentofte Hospital, Denmark; Tømrermester Jørgen Holm og Hustru Elisa F. Hansens Mindelegat, Denmark (20006-1846); Dansk Kræftforskningsfond, Denmark; Region Sjællands Sundhedsvidenskabelige Forskningsfond, Denmark (R19A283B198); Dansk Brystkirurgisk Selskabs legat, Denmark; Helsefonden, Denmark (20-B-0003). The funding sources had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

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Authors and Affiliations



All authors contributed to the study conception and design. All authors were involved in material preparation, data collection, analysis, or interpretation of the analyses. The first draft of the manuscript was written by CH and TT. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Christina M. S. Hassing.

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Competing interests

Ann Søegaard Knoop reports personal fees from Novartis, Roche, Merck, Daiichi Sankyo, Gilead Sciences, Pfizer, Eli Lilly. Furthermore, she has been national or site investigator for Daiichi Sankyo and Sanofi. Tove Tvedskov reports speaker honorariums from Roche, MSD and Pfizer. Anne-Vibeke Lænkholm reports institutional research grants from Novartis and Astra Zeneca (AZ). Anne-Vibeke Lænkholm reports personal fees for participation in advisory boards, Novartis and AZ and for a research collaboration with Veracyte. No other potential conflicts of interest were reported.

Ethical approval

This study was approved by the Regional Research Ethics Committee of the Capital Region of Denmark (H-18045702) and by the Regional Data Protection Agency (P-2019-124).

Informed consent

Exception for obtaining informed consent was given by the Regional Research Ethics Committee of the Capital Region of Denmark as the present study implied no health-related risks or discomfort for the involved patients.

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Hassing, C.M.S., Mejdahl, M.K., Lænkholm, AV. et al. Adjuvant chemotherapy in patients with ER-negative/HER2-negative, T1abN0 breast cancer: a nationwide study. Breast Cancer Res Treat 198, 103–112 (2023).

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