Abstract
Lobular primary breast cancer (PBC) histology has been proposed as a risk factor for contralateral breast cancer (CBC), but results have been inconsistent. We investigated CBC risk and the impact of systemic therapy in lobular versus ductal PBC. Further, CBC characteristics following these histologic subtypes were explored. We selected 74,373 women diagnosed between 2003 and 2010 with stage I-III invasive PBC from the nationwide Netherlands Cancer Registry. We assessed absolute risk of CBC taking into account competing risks among those with lobular (n = 8903), lobular mixed with other types (n = 3512), versus ductal (n = 62,230) histology. Hazard ratios (HR) for CBC were estimated in a cause-specific Cox model, adjusting for age at PBC diagnosis, radiotherapy, chemotherapy and/or endocrine therapy. Multivariable HRs for CBC were 1.18 (95% CI: 1.04-1.33) for lobular and 1.37 (95% CI: 1.16-1.63) for lobular mixed versus ductal PBC. Ten-year cumulative CBC incidences in patients with lobular, lobular mixed versus ductal PBC were 3.2%, 3.6% versus 2.8% when treated with systemic therapy and 6.6%, 7.7% versus 5.6% in patients without systemic therapy, respectively. Metachronous CBCs were diagnosed in a less favourable stage in 19%, 26% and 23% and less favourable differentiation grade in 22%, 33% and 27% than the PBCs of patients with lobular, lobular mixed and ductal PBC, respectively. In conclusion, lobular and lobular mixed PBC histology are associated with modestly increased CBC risk. Personalised CBC risk assessment needs to consider PBC histology, including systemic treatment administration. The impact on prognosis of CBCs with unfavourable characteristics warrants further evaluation.
Original language | English |
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Pages (from-to) | 3123-3133 |
Number of pages | 11 |
Journal | Cancer Medicine |
Volume | 12 |
Issue number | 3 |
Early online date | 20 Sept 2022 |
DOIs | |
Publication status | Published - Feb 2023 |
Bibliographical note
Funding Information:We thank the registration team of the Netherlands Comprehensive Cancer Organisation (IKNL) for the collection of data for the Netherlands Cancer Registry (NCR) as well as the IKNL staff for scientific advice. We would also like to thank all patients of whom we used the data and all clinicians involved in the care of these patients. We would like to thank Benjamin Y. Gravensteijn for his efforts in the statistical analysis in R.
Funding Information:
This work was supported by the Dutch Cancer Society/Alpe d'HuZes [A6C/6253].
Publisher Copyright:
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.