Abstract IA40: Obesity in breast and ovarian cancers: Racial/ethnic disparities

In the United States, obesity prevalence has been increasing steadily over the years in all racial/ethnic groups, but is markedly higher in African American (AA) (57.2%) and Hispanic women (46.9%), compared to non-Hispanic white (NHW) (38.2%) and NH Asian (12.4%) women (1). Obesity has been shown to affect cancer risk and progression and can also play a role on disease presentation, treatment efficacy and toxicity, and complicate clinical management of cancer due to obesity-related comorbidities such as hypertension and diabetes (2). Given the high prevalence of obesity in African American and Hispanic women and different metabolic consequences, understanding how it influences cancer risk, detection, disease presentation, clinical management, and progression and possible differences by race/ethnicity is crucial.

Breast cancer is the most common cancer among women worldwide, with wide variation in incidence and mortality across geographic regions. In the US, incidence rates have been historically higher in NHW women, but AA and Hispanic women tend to develop the disease at an earlier age and with more aggressive features. In particular, they are more likely to get ER- and triple-negative (TN) tumors, which are more difficult to treat and have worse prognosis. More recent data show that incidence rates in NHW and AA women converged in 2012 due to an increase in incidence in AA women and relatively stable incidence in NHW women³. Death rates are higher in AA than in NHW women, and this mortality difference has been widening over time. Causes of these disparities in risk and survival are likely to be multifactorial, and obesity has been implicated. There is strong evidence, mostly from studies conducted in NHW women, that obesity and weight gain during adulthood are associated with increased risk of postmenopausal breast cancer, particularly among women not using menopausal hormone therapy (4). Obesity during adolescence and young adulthood has been associated with reduced breast cancer risk (4). There is also growing evidence that the association differs by hormone receptor subtype, and that what we have historically known for the association of obesity and breast cancer only applies to ER+ tumors. Few studies have evaluated the association of obesity with the risk of ER- and TN breast cancer and the evidence is inconsistent. In the AMBER Consortium (5), which included four studies in AA women, we found that for ER+ breast cancer, obesity reduced risk for premenopausal women and increased risk for postmenopausal women. However, the risk of TN breast cancer was reduced for postmenopausal women with high BMI, but elevated for those with a high waist-to-hip ratio. One possible explanation for these findings is that TN tumors may be more influenced by components of the metabolic syndrome (central obesity, insulin resistance, dyslipidemia, hypertension) than by estrogens, as suggested by others (6). While more limited, there is growing evidence that obesity is associated with worse breast cancer outcomes, particularly for HR+ tumors (7), with no conclusive evidence on differences by race/ethnicity.

Ovarian cancer is the most lethal gynecologic cancer. With difficulties in early detection due to vague symptoms and the lack of effective screening tools, 60% of ovarian malignancies are detected when the disease is already at distant stage when 5-year survival is only 29% (8). Compared to NHW, incidence is lower in AA and Hispanic women, but survival is worse in both groups, after adjusting for age and stage (9) comparable to the incidence and mortality differences observed for breast cancer. Little is known about how the epidemiology of ovarian cancer may differ by race/ethnicity, but there is suggestive evidence that there may be differences in risk profiles, tumor subtype distribution, and clinical management, which may all be affected by obesity. For example, in KP ROCS (Kaiser Permanente Research on Ovarian Cancer Survival), a cohort study of ovarian cancer patients among Kaiser Permanente Northern California members, AA and Hispanic women were more likely to have chemotherapy dose reduction and unfavorable survival compared to NHW, after adjusting for clinical characteristics and detailed treatment information (10). Obesity was the most important predictor of chemotherapy dose reduction (11).

There is a general misconception that obesity is not prevalent among ovarian cancer patients. In KP ROCS, 58.5% of AA and 40.7% of Hispanic ovarian cancer patients were obese at diagnosis, compared to 29.5% of NHW (10). Fewer than 1% of Hispanic women and none of the AA women were underweight at diagnosis. In AACES (African American Cancer Epidemiology Study), a multisite case-control study of ovarian cancer in AA women, 61.8% of the cases were obese approximately one year before diagnosis (12). There is growing evidence that obesity increases ovarian cancer risk (13), but most studies were conducted in NHW women. In AACES, we found elevated risk of ovarian cancer with higher BMI and weight gain during adulthood among AA postmenopausal women (12). The impact of body mass index (BMI) on ovarian cancer survival is less clear, but meta-analyses and pooled analyses have suggested that obesity before an ovarian cancer diagnosis might be associated with lower survival, with weaker evidence for BMI at diagnosis. In KP ROCS we found that the association of prediagnosis and at-diagnosis obesity with ovarian cancer varied by stage, with lower survival among obese women with localized disease and better survival among obese women with late-stage disease (14). We found no major differences by race/ethnicity in the impact of obesity on survival, but statistical power was limited as analyses included few AA and Hispanic women.

Conclusion: There is growing evidence that higher body fatness is associated with increased breast and ovarian cancer risk and worse outcomes after diagnosis with these cancers, but there are multiple research gaps to fully understand these associations (15). Better methods are needed to measure adiposity, but tools also need to be feasible for use in population-based studies to allow the inclusion of large and multiethnic populations. The role of obesity on cancer risk and survival needs to be evaluated by tumor subtype, menopausal status, use of menopausal hormone therapy, and racial/ethnic subgroup with consideration of country of origin and genetic ancestry. The impact of body fatness during critical exposure windows and the impact of weight changes throughout the cancer continuum are also poorly understood. Cancer survival studies need to take into account prognostic factors, including chemotherapy dosing and obesity-related comorbidities that can have a direct impact on cancer clinical management and survival.

References

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Citation Format: Elisa V. Bandera. Obesity in breast and ovarian cancers: Racial/ethnic disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA40.