Highlights From the 2016 AACR Annual Meeting


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This year’s Annual Meeting of the American Association for Cancer Research (AACR) featured outstanding research in the field of cancer, as well as an inspiring talk by Vice President Joe Biden (see the May 10 issue of The ASCO Post). Here are some summaries of studies that warrant attention; they focus on lifestyle factors in cancer epidemiology, the timeliness of radiation therapy in women with ductal carcinoma in situ, and cardiac toxicity associated with targeted therapies for hematologic malignancies.

Benefit of Low-Fat Diet Continues


We found that a sustained low-fat diet increased the survival rates among postmenopausal women after a breast cancer diagnosis.
— Rowan Chlebowski, MD, PhD

Women randomized to a dietary intervention with a low-fat eating pattern for approximately 8 years had lower incidence of deaths after breast cancer compared with women who had not followed the dietary regimen, according to Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center.1 The reduction was due in part to better survival following breast cancer diagnosis.

An association between dietary fat intake and breast cancer outcome has been suggested by many studies, but observational findings have been inconclusive. The Women’s Health Initiative randomized 48,835 postmenopausal women to receive a low-fat diet (n = 19,541) or their usual diet (n = 29,294). The low-fat dietary pattern intervention involved nutritionist-led group sessions that sought to reduce fat intake (20% of calories from fat) and increase the consumption of fruits and vegetables (target 5/d) and grains (target 6/d).

After approximately 8 years, 1,767 of the women were diagnosed with breast cancer, including 672 in the intervention group and 1,095 in the control group. Those on the low-fat diet reported significantly reduced calories from fat and significantly increased consumption of fruits, vegetables, and grains, compared with the control group. While weight loss was not an intended goal, body weight was significantly lower in the dietary group.

Among the 1,767 breast cancer cases, during the intervention period, there were 88 deaths from breast cancer and 134 deaths after breast cancer; these deaths were 32% less (P = .09) and 35% less (P = .02) in the low-fat diet group than in the control group, respectively. Overall survival at 10 years was 82% and 78%, respectively—a 20% reduction in mortality (P = .02) in the low-fat group. Cardiovascular mortality, in particular, was reduced in this arm.

“This was the first time we had examined the deaths after breast cancer among this group, and we found that a sustained low-fat diet increased the survival rates among postmenopausal women after a breast cancer diagnosis,” said Dr. Chlebowski. “The study also suggests that women would need to remain on the low-fat diets to maintain the benefits of the dietary intervention.”

Physical Activity Reduces Risk of Prostate Cancer Death

Engaging in higher levels of recreational physical activity before and after diagnosis of prostate cancer is associated with a marked improvement in survival among patients with prostate cancer. Conversely, the amount of time spent sitting (ie, sedentary time) was not associated with prostate cancer–specific mortality. These were the findings of a large prospective cohort study.2

Ying Wang, PhD

Ying Wang, PhD

“Our results support evidence that prostate cancer survivors should adhere to physical activity guidelines and suggest that physicians should consider promoting a physically active lifestyle to their prostate cancer patients,” said lead author Ying Wang, PhD, Senior Epidemiologist in the Epidemiology Research Program at the American Cancer Society (ACS) in Atlanta.

The study included 10,067 men who were diagnosed with nonmetastatic prostate cancer between 1992 and 2011; all subjects participated in the Cancer Prevention Study II Nutrition Cohort. During follow-up until 2012, 600 prostate cancer deaths were recorded.

The metabolic equivalent hours per week of activity were calculated both before and after receiving a prostate cancer diagnosis based on self-reports on the amount of time spent in physical activity (walking, dancing, bicycling, aerobics, jogging or running, tennis, or racquetball, and lap swimming).

In a multivariable-adjusted analysis, exercising for 17.5 or more metabolic equivalent hours per week before diagnosis was associated with a 30% lower risk of prostate cancer–specific mortality compared with exercising for fewer than 3.5 metabolic equivalent hours per week. The cutoff of 17.5 metabolic equivalent hours per week is equivalent to 2.5 hours of walking per week or twice that of the minimum level of physical activity recommended by the guidelines for cancer survivors, said Dr. Wang, whereas fewer than 3.5 metabolic equivalent hours per week represents less than 1 hour of moderate-paced walking per week.

In post diagnosis, men who exercised 17.5 or more metabolic equivalent hours per week had a 34% lower risk of dying of prostate cancer compared with those who exercised fewer than 3.5 metabolic equivalent hours per week. Survival benefit was also observed in patients who increased their prediagnostic level of physical activity after their diagnosis.

Forty percent of participants listed walking as their only form of recreational physical activity. Walking only for 4 to 6 hours per week before diagnosis of prostate cancer was associated with a 33% reduced risk of prostate cancer–specific mortality, and walking for 7 or more hours per week before diagnosis was associated with a 37% lower risk. No statistically significant association was found for walking after diagnosis.

Ductal Carcinoma in Situ Merits Timely Radiation

Delaying radiation therapy beyond 8 weeks after breast-conserving surgery or not receiving any radiation increased the risk of developing invasive breast cancer for women with ductal carcinoma in situ, according to a study presented at the 2016 AACR Annual Meeting.3

Ductal carcinoma in situ is common, and guideline-recommended therapy includes breast-conserving surgery plus radiation, breast-conserving surgery alone, or total mastectomy. Some women with ductal carcinoma in situ will go on to develop invasive breast cancer, but thus far, there is no biomarker that can predict which women are at risk for more serious cancer.

Ying Liu, MD, PhD

Ying Liu, MD, PhD

“This study shows that it is important for women to understand the benefits of receipt of timely radiation therapy after breast-conserving surgery,” said lead author Ying Liu, MD, PhD, Instructor of Surgery at Washington University School of Medicine and researcher at Siteman Center in St. Louis.

The study was based on 5,916 women in the Missouri Cancer Registry who developed a first primary with ductal carcinoma in situ between 1996 and 2011 and received breast-conserving surgery. Among these women, 1,053 (17.8%) received radiation 8 weeks or more after surgery, or “delayed radiation.” Another 1,702 women (29.9%) did not receive any radiation as part of therapy for ductal carcinoma in situ. The remaining 53.4% received “timely” radiation, i.e., within 8 weeks of surgery.

During 72 months of follow-up, 3.1% of women developed an ipsilateral breast tumor (invasive or in situ). An analysis adjusted for propensity score based on age, race, tumor size, and grade showed that the risk of developing an ipsilateral breast tumor was 26% higher for women who delayed radiation and 35% higher who did not receive radiation therapy as treatment for ductal carcinoma in situ.

Radiation delays were significantly more common among African Americans, single women, Medicaid recipients, those with larger ductal carcinoma in situ tumors, and patients who were diagnosed more recently.

Unanticipated Cardiac Toxicity

An ongoing study has found that several targeted therapies used to treat hematologic malignancies are associated with unintended cardiac toxicity in some patients, and when it develops, it can lead to cardiac-related mortality.4 The good news is that in most cases, the cardiac toxicity is reversible.


The type of cardiac toxicity associated with targeted therapies for hematologic malignancies is different from the situation with anthracyclines, where cardiac toxicity is anticipated and is dose-dependent.
— Jan Moreb, MD

“Unanticipated cardiac toxicity occurred in about 4% of patients with hematologic malignancies over a 10-year period. This was not dose-dependent. It was caused by the targeted therapy,” said lead author Jan Moreb, MD, of the University of Florida, Gainesville.

“Most patients [who develop cardiac toxicity on targeted therapy] do well with cardiac drug regimens that lead to stable compensated cardiac function, with objective improvement in left ventricular ejection fraction seen in about 25%. Two patients had non ST-segment elevated myocardial infarction without coronary artery disease or significant drop in left ventricular ejection fraction,” he continued.

The retrospective study is a joint effort by hematologists/oncologists, cardiologists, and pharmacists at the University of Florida in Gainesville. So far, they have analyzed records of 820 patients with hematologic malignancies and cardiac problems treated between 2005 and 2014.

Forty-four patients were identified with cardiac toxicity and received any of the following drugs: tyrosine kinase inhibitors such as imatinib, dasatinib (Sprycel), ponatinib (Iclusig), and nilotinib (Tasigna); proteasome inhibitors such as bortezomib (Velcade) and carfilzomib (Kyprolis); immunomodulatory agents such as thalidomide (Thalomid), pomalidomide (Pomalyst), and lenalidomide (Revlimid); monoclonal antibodies such as rituximab (Rituxan), alemtuzumab (Campath); and hypomethylating agents such as azacitidine and decitabine.

Cardiac toxicity, defined as left ventricular ejection fraction < 50%, arrhythmia, or ischemic cardiovascular event, was confirmed in 44 of these patients. Ten patients with preexisting cardiac disease were excluded from the analysis. Of the 34 remaining patients (~4% of 820 total patients studied), 17.6% died of cardiac causes.

“The type of cardiac toxicity associated with targeted therapies for hematologic malignancies is different from the situation with anthracyclines, where cardiac toxicity is anticipated and is dose-dependent,” Dr. Moreb said.

The ongoing study will attempt to identify risk factors for cardiac toxicity in this population. “Considering the generally good outcomes seen regarding the cardiac toxicity in this setting and the great benefit of these targeted therapies, I would still recommend including these agents in treatment,” Dr. Moreb commented. Nevertheless, for now, oncologists should be alert to the possibility of cardiotoxicity in this patient population. ■

Disclosure: Dr. Chlebowski is a consultant for Novartis, Genentech, Amgen, Genomic Health, and Novo Nordisk and is on the speakers bureau for Novartis and Genentech. Drs. Wang and Moreb reported no potential conflicts of interest.

References

1. Chlebowski R, Aragaki AK, Anderson GL, et al: Low-fat dietary pattern and breast cancer mortality in the Women’s Health Initiative randomized trial. 2016 AACR Annual Meeting. Abstract CT043. Presented April 18, 2016.

2. Wang Y, Jacobs EJ, Gansler T, et al: Physical activity, sitting time and prostate cancer specific mortality: The Cancer Prevention Study II nutrition cohort. 2016 AACR Annual Meeting. Abstract 1736. Presented April 18, 2016.

3. Liu Y, Yun S, Lian M, et al: Radiation therapy delay and risk of ipsilateral breast tumors in women with ductal carcinoma in situ. 2016 AACR Annual Meeting. Abstract 2576. Presented April 18, 2016.

4. Moreb JS, Mohammad H, McCullough L, et al: Incidence and natural history of cardiovascular toxicity associated with biologic and targeted therapies used in hematologic malignancies. 2016 AACR Annual Meeting. Abstract 1431. Presented April 18, 2016.


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