Breast cancer is the second-leading cause of cancer mortality among women in the U.S., according to the American Cancer Society. Given this trend, insights into the variables related to reducing breast cancer mortality in patients are essential.
Modifiable practices that can be implemented by patients with cancer include dietary changes. One potentially modifiable dietary component is the consumption of sugar-sweetened beverages (SSB) and artificially sweetened beverages (ASB). According to the Global Burden of Disease 2017 risk collaborators, worldwide consumption of sugar-sweetened beverages has dramatically increased in the last several decades (Lancet 2018; https://doi.org/10.1016/S0140-6736(18)32225-6).
Research has also demonstrated an association between excessive consumption of sugar-sweetened beverages and cardiometabolic health (Nutrients 2019; doi: 10.3390/nu11081840). However, there is mixed evidence regarding the association with consumption of SSBs and ASBs with cancer (Nutrients 2021; doi: 10.3390/nu13020516). More specifically, there have only been a few observational studies addressing the associations between SSB and ASB intakes and breast cancer.
* A 2020 French prospective study reported that women in the highest quartile of total sugar intake were 51 percent more likely to develop breast cancer than those in the lowest quartile (Am J Clin Nutr 2020; https://doi.org/10.1093/ajcn/nqaa246).
* A study from the University of Buffalo finds that women drinking non-diet soda 5 times or more per week had a 62 percent higher likelihood of dying from any causes, and were 85 percent more likely to die from breast cancer specifically (Cancer Epidemiol Biomarkers Prev 2021; https://doi.org/10.1158/1055-9965.EPI-20-1242).
With the indicative evidence that SSB and ASB consumption may raise the risk of breast cancer incidence and mortality, understanding their possible effect on breast cancer prognosis is an important public health interest. To address these knowledge gaps, Romanos-Nanclares, et al, conducted a study to evaluate associations between consumption of SSBs and ASBs and risks of total and subtype-specific breast cancer. The findings were published in the Journal of Nutrition (2021; https://doi.org/10.1093/jn/nxab172).
In the study, the researchers utilized data from two large, prospective U.S. cohorts of young women with detailed and updated dietary intake assessments: the original Nurses' Health Study (NHS) (1980-2016) and Nurses' Health Study II (NHSII) (1991-2017). Both studies, based at Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, collected information on health-related factors and medical history. Diets were evaluated with a validated food frequency questionnaire and administered in the NHS in 1980, 1984, 1986, and every 4 years subsequently and in the NHSII in 1991 and every 4 years subsequently.
The team followed 82,713 women from the NHS and 93,085 women from the NHSII. Invasive breast cancer cases were identified through self-report questionnaires or the National Death Index and confirmed by medical records. Intakes of SSBs and ASBs from food frequency questionnaires were cumulatively averaged and investigated for associations with incident breast cancer cases and subtypes using Cox regression models. Additionally, associations stratified by BMI, physical activity, menopausal status, and alcohol intake were also analyzed.
Overall, the researchers identified 11,379 cases of breast cancer incidence among 175,798 women during 4,655,153 person-years of follow-up. No significant associations of SSB or ASB intake with total breast cancer risk were observed: pooled HRs comparing extreme categories (>= 1/day compared with <1/month) were 1.03 (95% CI: 0.95-1.12) and 0.96 (95% CI: 0.91-1.02), respectively.
However, a suggestive interaction by BMI using pooled data (P= 0.08) revealed that consumption of SSBs was associated with a slightly higher risk of breast cancer among lean women (HR, 1.06; 95% CI: 1.01-1.11), which was independent of weight changes and other established dietary and non-dietary breast cancer risk factors.
Additionally, the team discovered a modest inverse association between ASB intake and the risk of luminal A breast tumors, particularly in obese women. In the pooled, fully adjusted analysis, compared to infrequent consumers (<1/month), those who consumed >=1 serving of ASBs per day had a lower risk of luminal A breast tumors (HR, 0.90; 95% CI: 0.80-1.01; P=0.02).
Oncology Times chatted with study author, Andrea Romanos-Nanclares, PhD, for additional thoughts on their work. She is currently a Postdoctoral Research Fellow at the Channing Division of Network Medicine at Brigham and Women's Hospital Department of Medicine and Harvard Medical School. Her research focuses on exploring the association between diet, metabolomics, and breast cancer development within the framework of the Nurses' Health Studies.
Oncology Times: Were any of the findings of the study surprising for you?
Romanos-Nanclares: "In our study, consumption of sugar-sweetened beverages was modestly associated to breast cancer risk independently of adiposity pathways, which I found quite intriguing. In other words, the association between sugar-sweetened beverages and breast cancer may also be explained by other mechanisms, such as activation of the insulin signaling pathway, as well as oxidative stress and inflammation.
"Another thought-provoking finding was the modest inverse association between artificially sweetened beverages (ASBs) and the risk of luminal A breast tumors, particularly among obese women. Because this is the first evaluation of ASBs intake and subtype-specific breast tumors, additional high-quality, long-term research is needed to confirm this finding and understand the mechanisms of action of ASBs."
Oncology Times: The results of this study contrast findings of other reports, such as The Western New York Exposures and Breast Cancer (WEB) Study, which shows strong evidence of mortality risk associated with the consumption of sugar-sweetened beverages (SSB)(Cancer Epidemiol Biomarkers Prev 2021; doi: 10.1158/1055-9965.EPI-20-1242). What are some possible explanations for the inconsistent findings between SSBs and breast cancer in the epidemiologic literature?
Romanos-Nanclares: "Although we only explored the associations of SSBs and ASBs with breast cancer incidence, a team from the Nurses' Health Studies, including Heather Eliassen, ScD, previously reported on the association between post-diagnostic SSB and ASB consumption with mortality among women with breast cancer (2021; https://doi.org/10.1002/cncr.33461).
"In fact, consistent with the findings from the WEB study, higher post-diagnostic SSBs consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes. In the latter study, 2,482 deaths were prospectively documented, including 1,050 deaths from breast cancer. Interestingly, replacement of SSBs with non-caloric beverages including coffee, tea, and water was associated with a lower risk of breast cancer-specific and all-cause mortality.
"In the literature, inconsistent findings between SSBs and breast cancer incidence likely are due to heterogeneity across studies (i.e., differences in population characteristics, study design, and analysis strategies). Nonetheless, most studies that evaluated this association were adjusted for BMI, which suggests that pathways other than body weight gain might be implicated in the associations."
Oncology Times: Recent statistics show that breast cancer has become the leading cause of cancer death for Black women. In your study, were you able to observe any differences in the association between sugar-sweetened beverages and cancer mortality between races?
Romanos-Nanclares: "It should be noted that women participating in the Nurses' Health Studies were mostly Caucasian and had a slightly higher socioeconomic status than the general population (reflecting the demographics of the nursing profession at the time of enrollment in the 1970s and 1980s), which may have initially affected generalizability.
"However, this enhanced the internal validity of our study because of the homogeneity of the population in terms of health knowledge and commitment to research contributing to high-quality and complete self-reported health data, as well as high follow-up rates. Also, the underlying biologic mechanisms were not likely to differ substantially by race neither in our incidence analysis nor in the survival analysis performed by Farvid, et al (Cancer 2021; https://doi.org/10.1002/cncr.33461)."
Oncology Times: What are the implications of this study? Is there any utility in continuing to investigate the effect of SSBs on breast cancer outcomes?
Romanos-Nanclares: "The implications of the study are clear as the world grapples with rising obesity and chronic disease burdens: we should try to minimize intake of sugar-sweetened beverages while we continue to research the influence of sugar-sweetened beverages on health outcomes, particularly, obesity-related tumors.
"Translating the findings into smart, simple, scalable, and sustainable recommendations for breast cancer prevention require further confirmation through carefully well-conducted prospective cohort studies with repeated measures. However, there are many health benefits to be gained by reduction in SSB consumption, and the possible benefit for breast cancer may provide additional impetus for women to change their habits.
"SSBs are generally consumed as a discrete food, and not as ingredient; they are habitual and not seasonal and are a good and practical measure to study the relation between diet and disease, being one of the most reliably reported foods on food-frequency questionnaires. Moreover, major research gaps exist with regard to suitable alternative beverages, including the health effects of consuming ASBs over the life course, which are not metabolically inert. Our finding of a suggested inverse association between ASBs and one subtype of breast cancer deserves further investigation for confirmation.
"Additional questions raised by this finding include: What type(s) of artificial sweeteners are driving this potential association? By what mechanisms? Is the food matrix in which the artificial sweetener is included more important than the sweetener itself? Are synergistic effects between multiple additives in the same beverage feasible?
"Overall, our findings shed new light on other less frequently studied diseases but of high public health relevance, therefore reinforcing the current message and serving as important steps in swapping social norms surrounding beverage habits."
Dibash Kumar Das is a contributing writer.
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