Precis:
The data of Sella et al and UK Biobank suggest that mechanisms of body weight regulation could interact with breast cancer genetics to promote or inhibit premenopausal breast cancer. Such interaction is already known to occur in post-menopausal breast cancer.
Keywords: neoplasm, weight, body mass, thermogenesis, weight regulation
Lay summary:
Mechanisms of body weight regulation could interact with breast cancer genetics to promote or inhibit premenopausal breast cancer. Such interaction is already known to occur in post-menopausal breast cancer.
According to Sella et al., the mean weight and BMI of young breast cancer survivors aged 40 and younger slightly increased over time (Cancer, July 1, 2022). At three years after diagnosis, one-third of women experienced clinically significant weight gain that was not substantially correlated with the type of treatment or menopause brought on by treatment.
We examined data from UK Biobank to compare weight gain of young breast cancer patients with young women who did not have breast cancer.1 Our UK Biobank application was approved as UKB project 57245 (S.L., P.H.R.). In our analysis, self-reported weight change data were used. Baseline weight change was defined as weight change one year prior to baseline. No change, gained weight, lost weight, do not know, or prefer not to answer could be given as a weight change response. Amount of weight change was not recorded.
We identified 30 women with breast cancer and 1287 women without breast cancer under age 45. Of the women with breast cancer, 23 (76.7%) had no gain in weight, while 7 (23.3%) gained weight. Of the women without breast cancer, 732 (56.9%) had no gain in weight, while 555 (43.1%) gained weight. This variability was significant (p = 0.039, two tailed Fisher exact test).
Women less than age 45 approaching menopause gain weight,2 as did 43.1 % of the women without breast cancer. But of the breast cancer patients in the same age group only 23.3% gained weight, while others did not gain weight.
Weight gain after breast cancer diagnosis is an unfavorable prognostic sign.3 Our finding of weight variability in women under 45 with breast cancer may indicate a fundamental alteration or derangement in body weight regulation in these women, a complex process involving food intake, nutrient turnover, thermogenesis, and body fat stores. Extensive feedback networks are involved.4 A weakness in our analysis is that we do not know whether mastectomy might have been responsible for lack of weight gain in some of the breast cancer patients.
Nevertheless, the data of Sella et al and UK Biobank suggest that mechanisms of body weight regulation could interact with breast cancer genetics to promote or inhibit premenopausal breast cancer. Such interaction is already known to occur in post-menopausal breast cancer.5 Further studies are warranted.
Acknowledgments
This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai.
Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award numbers S10OD018522 and S10OD026880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Footnotes
Conflicts of interest: none
Ethics approval: UK Biobank has approval from the Northwest Multi-center Research Ethics Committee (MREC), which covers the UK. It also sought the approval in England and Wales from the Patient Information Advisory Group (PIAG) for gaining access to information that would allow it to invite people to participate. PIAG has since been replaced by the National Information Governance Board for Health & Social Care (NIGB). In Scotland, UK Biobank has approval from the Community Health Index Advisory Group (CHIAG).
Note: The authors of the original article were invited to respond, but did not feel a response was necessary given the letter did not ask any questions of them.
Contributor Information
Steven Lehrer, Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
Peter H. Rheinstein, Severn Health Solutions, Severna Park, Maryland.
References
- 1.Bycroft C, Freeman C, Petkova D, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. Oct 2018;562(7726):203–209. doi: 10.1038/s41586-018-0579-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Davis SR, Castelo-Branco C, Chedraui P, et al. Understanding weight gain at menopause. Climacteric. 2012;15(5):419–429. [DOI] [PubMed] [Google Scholar]
- 3.Kroenke CH, Chen WY, Rosner B, Holmes MD. Weight, weight gain, and survival after breast cancer diagnosis. Journal of clinical oncology. 2005;23(7):1370–1378. [DOI] [PubMed] [Google Scholar]
- 4.Martinez JA. Body-weight regulation: causes of obesity. Proceedings of the nutrition society. 2000;59(3):337–345. [DOI] [PubMed] [Google Scholar]
- 5.Suga K, Imai K, Eguchi H, Hayashi Si, Higashi Y, Nakachi K. Molecular significance of excess body weight in postmenopausal breast cancer patients, in relation to expression of insulin‐like growth factor I receptor and insulin‐like growth factor II genes. Japanese journal of cancer research. 2001;92(2):127–134. [DOI] [PMC free article] [PubMed] [Google Scholar]