Risk of metachronous contralateral breast cancer in patients with primary invasive lobular breast cancer: Results from a nationwide cohort

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.

Impute‐then‐exclude versus exclude‐then‐impute: Lessons when imputing a variable used both in cohort creation and as an independent variable in the analysis model

“…Many cancer studies exclude patients with stage IV cancers, as these patients have a prognosis that is substantially worse than patients with non-stage IV cancers. [3][4][5][6][7] Thus, cancer stage is often used as an inclusion/exclusion criterion when creating a study sample. In the study sample, cancer stage can then be used as an exposure variable in the subsequent analysis model that is of scientific interest.…”

“…Stage IV denotes a cancer that has spread to distant parts of the body. Many cancer studies exclude patients with stage IV cancers, as these patients have a prognosis that is substantially worse than patients with non‐stage IV cancers 3‐7 . Thus, cancer stage is often used as an inclusion/exclusion criterion when creating a study sample.…”