“ Our study demonstrates a higher prevalence of prior breast cancer in patients with GC compared with patients with other BTC subtypes across both training and validation cohorts .”
BUFFALO, NY — October 1, 2026 — A new research paper was published in Volume 13 of Oncoscience on September 17, 2026, titled “ Association between breast cancer and gallbladder cancer: Evidence from two independent biliary tract cancer cohorts .”
The study found that a history of breast cancer was more common among patients with gallbladder cancer (GC) than among those with other biliary tract cancer (BTC) subtypes in two independent cohorts. The findings point to a possible association between the two malignancies but do not establish that breast cancer causes or directly increases the risk of gallbladder cancer.
The research was led by co-first authors Mara Persano and Margherita Rimini. Persano is affiliated with the Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy , and the Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy . Rimini is affiliated with the Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital . Rimini is also the corresponding author.
Biliary tract cancers are a heterogeneous group that includes intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. These tumors differ in their epidemiology, clinical behavior and molecular characteristics. Because some genetic alterations implicated in breast cancer, including HER2 and BRCA1/2-related pathways, have also been identified in biliary tract cancers, the researchers investigated whether a history of breast cancer was associated specifically with gallbladder cancer rather than with BTC more broadly.
The retrospective multicenter analysis included 1,687 patients with BTC from three centers in Italy and Spain. A training cohort included 204 patients treated at San Raffaele in Milan between 2021 and 2023, while an independent validation cohort included 1,483 patients from the Vall d’Hebron Institute of Oncology in Spain and Veneto Institute of Oncology in Italy between 2015 and 2023.
In the training cohort, 25.7% of patients with gallbladder cancer had a history of breast cancer, compared with 3.5% of patients with other BTC subtypes. This corresponded to an odds ratio of 9.40. The association was reproduced in the larger validation cohort, where previous breast cancer was identified in 5.1% of patients with gallbladder cancer compared with 2.4% of those with other BTCs, corresponding to an odds ratio of 2.18.
Across the two cohorts, 58 patients had diagnoses of both breast cancer and BTC. Breast cancer was diagnosed first in 54 of these patients, or 93.1%. The median interval between the two cancer diagnoses was approximately seven years. The authors note that this sequence could partly reflect the fact that breast cancer is substantially more common and generally occurs at a younger age than BTC. Therefore, the temporal relationship alone does not demonstrate a shared biological cause.
Among patients for whom breast cancer characteristics were available, most tumors were hormone receptor-positive and classified as luminal A or luminal B. This observation led the researchers to consider whether hormonal signaling could contribute to the association. Estrogen and progesterone receptors have previously been described in gallbladder lesions, and estrogen-related signaling has been implicated experimentally in gallbladder cancer biology. However, the authors emphasize that evidence for a hormonal connection remains limited and inconclusive.
The researchers also explored potential molecular similarities. Genomic profiling was available for a relatively small subgroup of gallbladder cancers. Alterations involving HER2, MDM2, CDKN2A, MTAP, ARID1A and CDKN2B occurred more frequently among patients with a history of breast cancer, while STK11 alterations were found only among those without such a history. None of these differences reached statistical significance, meaning that the genomic findings should be considered exploratory rather than evidence of a shared molecular mechanism.
The study also raises the possibility of shared inherited susceptibility. Germline alterations in genes such as BRCA1, BRCA2, BAP1 and STK11 are associated with hereditary cancer syndromes, and BRCA1/2 are well established in inherited breast cancer susceptibility. However, germline testing was not available in the current study, so whether inherited genetic factors contribute to the observed breast–gallbladder cancer association remains unknown.
“ Future studies starting with breast cancer populations and investigating their subsequent risk of BTC, particularly GC, are warranted .”
The study has several limitations. Its retrospective design could introduce inaccuracies in medical histories, and biological information was incomplete for some breast cancer cases. Genomic profiling was not performed uniformly across BTC samples, the molecular analyses involved small numbers of patients, and germline testing was unavailable. The different frequencies of breast cancer observed in the training and validation cohorts also underscore the need for additional studies before the magnitude of the association can be established.
Overall, the findings provide evidence of a reproducible association between prior breast cancer and gallbladder cancer within two independent BTC cohorts. Hormonal signaling, inherited susceptibility and overlapping molecular pathways are possible explanations, but none has yet been established. Future studies beginning with breast cancer populations will be needed to determine whether survivors have an increased subsequent risk of gallbladder cancer and whether the findings could eventually inform risk stratification or long-term surveillance.
DOI: https://doi.org/10.18632/oncoscience.674
Correspondence to: Margherita Rimini – rimini.margherita@hsr.it
Abstract video: https://www.youtube.com/watch?v=BAuHB6WKmdc
Keywords: gallbladder cancer, breast cancer, biliary tract cancer
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Association between breast cancer and gallbladder cancer: Evidence from two independent biliary tract cancer cohorts
17-Sep-2026
Andrea Casadei Gardini reports consulting fees from AstraZeneca, Bayer, BMS, Eisai, Incyte, Ipsen, IQVIA, MSD, Roche, and Servier; lecture fees from AstraZeneca, Bayer, BMS, Eisai, Incyte, Ipsen, Roche, and Servier; travel expenses from AstraZeneca; research grants (to the institution) from AstraZeneca, and Eisai. Sara Lonardi reports personal honoraria as invited speaker from Amgen, Astra Zeneca, Bristol-Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre-Fabre, Roche, and Servier; participation in advisory board for Amgen, Astellas, Astra Zeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, GSK, Incyte, Lilly, Merck Serono, MSD, Servier, Takeda, Rottapharm, Beigene, Fosun Pharma, and Nimbus Therapeutics. Mara Persano, Margherita Rimini, Antonio De Rosa, Daniel López-Valbuena, Mario Domenico Rizzato, Florian Castet, Caterina Soldà, Gloria Castillo, Teresa Macarulla, Silvia Camera, Francesco Vitiello, Federico Rossari, Federica Pedica, Francesca Ratti, Francesco De Cobelli, and Paolo Giorgio Arcidiacono declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.