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.

Summary Two hundred and twenty-two patients with advanced breast cancer were randomised in two separate trials of similar design to either concomitant combination treatment or sequential use of the same drugs given as single agents changed only at disease progression. Both trials used cyclophosphamide, methotrexate, 5-fluorouracil and prednisone; the WCSG using triiodothyronine and the SECSG using vincristine as the remaining agent. A common data base was generated for these trials and combined for analysis. Considering all patients, combination treatment was associated with a significantly increased response (46 versus 25%, P<0.05) but not survival improvement. For the 141 patients without liver involvement, survival was closely comparable in both treatment arms. Combination therapy did result in significant survival benefit for patients with liver involvement (P<0.05). These studies demonstrate: (1) in the majority of breast cancer patients, sequential single agent therapy can result in survival comparable to combination treatment; and (2) sole consideration of response frequency does not represent the optimal criterion to compare therapeutic approaches in advanced breast cancer.

For breast cancer ASCO abstracts in the past decade, we determined the following: (1) adjuvant trials have not infrequently supported study hypotheses; and (2) advanced-disease trials have consistently failed to identify new approaches with a significant impact on survival. These results suggest that a critical process evaluation of current policy and procedures involved in directing breast cancer research is warranted, especially for strategies in advanced disease.

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