Synchronous Bilateral Breast Cancers Are Distinct Diseases

Synchronous bilateral breast cancers (sBBC) have been associated with poorer outcomes as compared with unilateral cancer, but immune infiltration within this disease as well as its response to treatments have yet to be fully determined. To analyze somatic alterations, the immune microenvironment, and tumor evolution under treatment, Hamy and colleagues evaluated 313 paired invasive sBBC tumors and showed that a majority of tumor pairs (approximately 85%) were concordant in both clinical and pathologic patterns, while 15% were discordant pairs. Evaluation of immune infiltration revealed that discordant tumor pairs had a greater difference in tumor-infiltrating lymphocytes (TIL) between left and right tumors as compared with concordant subtypes, with TIL levels being shown to be affected by subtype of the contralateral tumor. Specifically, luminal breast cancers had lower TIL levels when the contralateral tumor was concordant, suggesting that TIL levels are not determined solely by local properties of the tumor microenvironment. Moreover, investigation into the effects of neoadjuvant therapy indicated that the pathologic complete response (pCR) rate was higher in luminal breast cancers when the contralateral pair was discordant. Further genomic analyses of 20 tumors from six patients with sBBCs that included samples from both left and right tumors before neoadjuvant chemotherapy (NAC) and after NAC demonstrated that somatic mutations and copy-number alterations were not shared between left- and right-side tumors of any patient. Additionally, no common clones were seen between bilateral samples in the same patient, suggesting that these tumors are not clonally related and their evolution under NAC does not lead to a common profile. Further transcriptomic analyses indicated that residual disease and the primary tumor are closer transcriptomically than the left and right tumors from the same patient. In summary, these results provide a comprehensive overview of sBBC, notably in terms of immune infiltration and response to treatment, and suggest that, as this disease was not found to be driven by a common genetic alteration, these tumor pairs should be considered singular entities before systemic treatment.

Hamy AS, Abécassis J, Driouch K, Darrigues L, Vandenbogaert M, Laurent C, et al. Evolution of synchronous female bilateral breast cancers and response to treatment. Nat Med 2023 Mar 6 [Epub ahead of print].

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