Abstract S5-04: Low-fat dietary pattern and breast cancer overall survival in the women's health initiative dietary modification randomized controlled trial

Abstract

Introduction: Among 48,835 postmenopausal women randomized in the Women's Health Initiative Dietary Modification (WHI DM) primary prevention trial, 1,767 women were diagnosed with breast cancer during the 8.3 years of dietary intervention. While differences were not statistically significant, there were fewer breast cancers diagnosed in the low fat dietary group women (HR 0.92 95% CI 0.84-1.01, P=0.09) with somewhat lower breast cancer mortality (HR 0.77 95% CI 0.48-1.22) than seen in control group women (JAMA 2006; 295:629). These findings were recently updated, and after 10.9 years (mean) post-diagnosis follow-up, breast cancer overall survival among these 1,767 women measured from diagnosis was greater in the dietary group (10 year survival, 82% vs 78%, 168 (2.24%) versus 319 (2.71%) deaths; HR 0.80 95% CI 0.66-0.97, P=0.02) (AACR Annual Meeting 2016, abstract CT0433, Clinical Trials Plenary Session). We now report low-fat dietary pattern influence on breast cancer overall survival in subgroups defined by breast cancer characteristics. Methods: The WHI DM trial, conducted at 40 US clinical centers, from1993-1998 enrolled 48,835 postmenopausal women, aged 50-79, without prior breast cancer, with normal mammogram and dietary fat intake >32% of total energy. Participants were randomly assigned to a dietary intervention group (40%, n=19,541) with goals of fat intake reduction to 20% of energy and increased fruits, vegetables and grain intake, or a usual diet control group (60%, n=29,294). As previously reported, the dietary modification program reduced fat intake, increased fruit, vegetable and grain intake and was associated with modest weight loss (all P< 0.001). The current secondary analysis outcome is breast cancer overall survival in subgroups defined by breast cancer characteristics for cases diagnosed during the dietary intervention period. Because of possible selection prior to breast cancer diagnosis, these analyses do not compare randomized outcomes. Therefore, careful attention is paid to control of risk factors for breast cancer in the analysis. Results: The examined subgroups included histology (ductal, lobular, other), estrogen receptor (ER) status (positive vs. negative by local laboratory), progesterone receptor (PR) status, HER2 status, triple negative (yes/no), stage (local, regional or distant), grade (well, moderately, poorly differentiated), tumor size (<1, 1- 2, >=2 cm), and nodal involvement (none, 1-3, 4+). None of the tests of interaction in subgroups were statistically significant. All subgroup hazard ratios (HR) were less than one except for ER negative cancers, triple negative cancers and those with 4+ positive lymph nodes. The results are suggestive of no influence of the low-fat dietary pattern on triple negative cancers (HR 1.64 95% CI 0.73-3.70 for triple negative vs. HR 0.73 95% CI 0.56-0.95 for other breast cancers, interaction P=0.06). Conclusion: Compared to a usual diet control group, women randomized to a dietary intervention group providing a low-fat dietary pattern had a significantly increased overall survival following a breast cancer diagnosis with the possible exception of those developing triple negative cancers. Citation Format: Chlebowski RT, Aragaki AK, Thomson CA, Anderson G, Manson JE, Simon MS, Rohan TE, Snetselar LG, Lane D, Barrington WE, Vitolins M, Womack C, Qi L, Hou L, Thomas F, Prentice RL. Low-fat dietary pattern and breast cancer overall survival in the women's health initiative dietary modification randomized controlled trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S5-04.

Weight loss and breast cancer incidence in postmenopausal women

“…After a mean 16.1-year cumulative follow-up with 3030 incident breast cancers, deaths after breast cancer were significantly reduced in the dietary intervention group, as measured from randomization 14 or from breast cancer diagnosis. 15 The current finding that weight loss determined over a relatively short 3 year period was associated with a significantly lower breast cancer incidence differs somewhat from findings previously reported from analyses in the separate WHI Clinical Trials population where weight loss was not associated with lower breast cancer incidence. 5 The demographic characteristics of the WHI Clinical Trial and Observational Study participants are comparable.…”

“…The association of weight loss with reduction in breast cancer risk in postmenopausal women is supported by findings from the WHI Dietary Modification Trial, 13 where 48,835 women were randomized to a dietary intervention based on a low-fat eating plan or to a usual diet control in a breast cancer primary prevention trial which were recently updated. 14,15 During the mean 8.5-year Cancer January 15, 2019 dietary intervention period, women in the dietary intervention group significantly reduced their fat intake compared with women in the usual diet control group, which was associated with a statistically significant (3%) weight loss. After a mean 16.1-year cumulative follow-up with 3030 incident breast cancers, deaths after breast cancer were significantly reduced in the dietary intervention group, as measured from randomization 14 or from breast cancer diagnosis.…”

Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer

“…M/D-driven tumors emerge in immunocompetent hosts via an ER-dependent oncogenic process, and progress as they evade immunosurveillance, culminating with the establishment of mammary tumors with a luminal B (highly proliferative HER2 − ER + VIM − ) phenotype that fails to convert into basal (ER − VIM + ) over time or upon treatment. Moreover, M/D-driven tumors developing in immunocompetent mice resemble human luminal B BCs as they exhibit common PI3KCA mutations 32 , poor immune infiltration coupled to limited sensitivity to ICBs 8 , and can be accelerated by nutritional interventions that have been epidemiologically linked to increased propensity for HR + BC in humans, such as a HFD 17 . One of the caveats of this model relates to the fact that while ER + BC is the most common form of BC in women, only a fraction of cases of ER + BC is linked to the use of progestins 11 .…”

“…Multiple epidemiological studies indicate that nutritional status has a major impact on BC incidence 17 , and it is now established that dietary interventions can mediate therapeutically relevant immunostimulatory effects 18 . We therefore analyzed the impact of nutritional interventions on M/D-driven carcinogenesis in WT C57BL/6 mice.…”

The Mediterranean Diet and Breast Cancer: A Personalised Approach

“…Interestingly, implementing a healthy dietary intervention could not only decrease incidence, but also indirectly improve outcome in breast cancer survivors by promoting weight loss and reducing obesity [26,27,28,29,30,31,32]. In this context, following a dietary pattern that consists of the basic principles of the Mediterranean-style diet is reported in several nutritional studies to be linked with better health outcomes [33] and has been suggested as a standard of nutritional quality due to its main components [34].…”