Breast Cancer and Fat – The Revisionist History of the Women’s Health Initiative

dietary fat and breast cancer

May 21, 2019 0 Comments

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Key Points:

  • The Women’s Health Initiative was a massive effort to test and assess an array of lifestyle recommendations in women.

  • A major goal was to assess the effect of a low-fat, high fruit and vegetable, and high grain diet coupled with intense counseling on multiple health variables without weight loss.

  • Women on the trial lost weight, likely from the intense intervention and counselling within the study, limiting conclusions about these lifestyle changes.

Last year another of the many publications from the Women’s Health Initiative (WHI) surfaced, further kicking the mummy trying to link breast cancer and dietary fat. This time around, the group found that a “low-fat dietary pattern” was associated with lower risk of death after breast cancer in the Women’s Health Initiative Randomized Controlled Dietary Modification Trial, which initially included over 48,000 women.1 The group is back at it, as they recently presented similar data at the annual American Society of Clinical Oncology meeting. Much like their recent manuscript, the unpublished work describes a 15% reduction in death from any cause after breast cancer diagnosis in the women in the intervention arm.

So, what can we take home from these results? A full description of the WHI is necessary before the media explosion can even be considered, and based on the WHI and several other similar studies, we can expect many more results similar to this latest presentation.

The WHI Was Testing Much More Than Dietary Fat and Breast Cancer

Around the time of the initial epidemiological studies revealing no link between breast cancer and dietary fat (and a potential detriment by replacing fat with carbohydrates) most of the available medical research, and especially lifestyle and disease prevention research, had focused on Caucasian males. The realization that women were being underrepresented within the research world provided the U.S. National Institute of Health ample reason to support efforts to level the research playing field. Establishing links between lifestyle habits and the most common cancer in women in the US provided the necessary fuel for the establishment of the WHI in 1991. Further emphasizing the strong push for female research, the National Institute of Health required the inclusion of women in clinical research during the same year. The WHI was composed of several clinical trials and an observational study, designed with the goal of studying cancer, cardiovascular disease, and osteoporosis – the three most common causes of death and illness in women. At a price tag of $625 million, the first massive study of its kind enrolled over 160,000 postmenopausal women from the ages 50-79, signaling to the medical world that massive prospective population studies were no longer an idea of the future.

For more than a decade the WHI accrued women and progressed as planned. By 2006, the study data had matured, and results of the several arms assessing the low-fat diet were reported in the Journal of the American Medical Association. These studies randomized over 48,000 women to one of two arms. The first group of women, known as the control arm, remained on their normal diet, though they received the diet-related educational material Dietary Guidelines for Americans, and kept a food diary. Furthermore, they filled out forms every 6 months to help track their food intake. The other group, known as the intensive behavior modification group, followed Plato-approved recommendations in the hopes that they would reduce their total fat intake to less than 20% of total calories. Furthermore, they were advised to increase their fruit and vegetable consumption to five or more servings per day and grains to at least six servings per day. To increase adherence, they attended frequent meetings with dietitians and nutritionists to discuss their food choices and to motivate them to make healthy changes. Physical activity levels were assessed at each clinician visit as well.

The trial was not testing a low-fat diet, per se, but rather a low-fat, high fruit and vegetable, and very high grain diet with lifestyle changes pounded into the heads of the women in the intervention arm. The intervention group decreased their fat intake by over 8%, while increasing their fruit, vegetable, and grain consumption. Not surprisingly, overall carbohydrate consumption increased significantly within the intervention group. Yet, unlike their behavior changes, healthful measurements were unchanged. The initial reports on the intervention’s impact on cardiovascular disease were somber: no significant reduction in the risk of coronary heart disease, stroke, or a combination of both was achieved from the dietary changes.2 It was felt, during this time, that a high-fat diet was largely responsible for obesity, and the merits of a low-fat diet would extend to weight loss as well. Yet, another study reported similarly negative results – the weight of women in the intervention arm remained similar as those women in the control.3  These results were published, also in the Journal of the American Medical Association, where the authors concluded that, “the results of this long-term trial of diverse postmenopausal women demonstrate that long-term recommendations to achieve a diet lower in total and saturated fat with increased consumption of fruits, vegetables, and whole grains, and without focus on weight loss, do not cause weight gain.” An ironic twist within the conclusions, perhaps attempting to soften the conclusions of a negative $625 million effort, applauded that the diet did not cause weight gain. These attempts at a silver lining, remarkably reminiscent of the conclusions from the earlier negative breast cancer studies by the group at Harvard, further revealed the anti-fat bias still deeply woven within the fabric of the medical establishment.

Regardless of whether this result was foreshadowing for just how deeply ingrained the bias was, or simply an attempt at doubling down to ensure taxpayers that their money was not misused, the conclusions morphed from testing the low-fat diet’s ability to provide weight loss, to ensuring that it does not cause it. Regardless of the failures of the $625 million-dollar diet, questions remained as to whether the diet could benefit more than just the pockets of the low-fat snack food industry during the past several decades. One in eight women were being diagnosed with breast cancer, and proponents remained hopeful that these dietary changes could help to lower the most common non-cutaneous malignancy in women. Breast cancer, much like cardiovascular disease and weight, was also unaffected by the dietary intervention.4 In keeping with past trends, the authors suggested in their conclusions that, perhaps a longer follow-up of these women would yield significant findings. Finally, colorectal cancer was also assessed within the WHI, and was consistent with other findings, as no reduction in incidence was seen in the intervention group.5 In a similar study, known as the Women’s Health Study, no link was found between dietary fat and colorectal cancer. However, they did find a potential link between fried foods and colorectal cancer, implicating the role of free radicals and polyunsaturated fat in cancer development.6

The negative results of the WHI were surprising on several accounts. At the time of the study, many had felt that these changes in isolation would positively affect multiple health markers. Yet, the intervention group was undergoing a barrage of changes, and many assumed the benefit would be additive, but at the very least, one modification would benefit their health. Finally, the intervention group was being followed intensely and counseled on healthy lifestyle changes, thus many felt that this counseling alone may provide the participants with motivation to follow a healthy lifestyle, regardless of what they were being counseled.

WHI and Fat and Breast Cancer – Stacking the Decks

(and pretending you didn’t)

Irrespective of the negative findings and high price tag, the study has garnered its share of criticism. A major concern that surfaced prior to any results, was that the study design would limit any tangible conclusions. The intervention included several changes, and though the goal was to reduce fat, it was replaced with fruits and vegetables, and carbohydrate-heavy grains, manufacturing an insulin-simulating diet to inhibit the ability of these women to lose weight amidst the multiple lifestyle changes. Furthermore, like others, this study was plagued heavily by intervention bias, or the potential ability of participants to derive benefit simply because they are contributing as part of a health intervention group. How much do monthly meetings with healthcare providers affect our motivations to be healthy? Additionally, how much does simply being part of the healthy diet intervention arm motivate us to change our behaviors, exercise more, or stop smoking? During my high school basketball games, we called this home team refereeing – where you set the deck so strongly against the opposing team that it is nearly impossible to lose (yes, Monaca, I am talking about you and yes, we still managed to beat you and eventually won the state championship). Along these lines, weight loss could reduce a woman’s risk of breast cancer, thus if these women lost weight and experienced a reduced risk of breast cancer, how would we know which factor was responsible, the lifestyle or weight loss? Critics argued that these issues begged the question whether any benefit could be attributed to the actual intervention, or whether the trial was simply stacking the deck against the control arm at the cost of $625 million. This common criticism continues to plague lifestyle intervention studies since, unlike randomized drug studies, providing a placebo is nearly impossible; participants are well aware of which arm of the study they are part of.

Yet, in an area of scientific research fraught with controversy, strong opinions, and beliefs that have been sown into our politics and religion since the dawn of agriculture – rightfully referred to as the dietary minefield – large prospective trials remain a financially feasible method of testing the impact of lifestyle changes in massive groups of people. A cost effectiveness study has even suggested that the WHI has saved taxpayers billions of dollars.7 Following in the footsteps of the behemoth WHI, two additional studies were established to analyze the impact of dietary fat reduction in women already diagnosed with breast cancer. Much like the WHI, the Women’s Healthy Eating and Living (WHEL) Randomized Trial placed women into a control and intervention arm. The latter group received intensive dietary counseling, including telephone calls, cooking classes, and newsletters promoting five servings of vegetables per day with 16 oz. of vegetable juice, three servings of daily fruit, 30 grams of daily fiber, and the reduction of dietary fat to 15% to 20% of total energy intake. Much like in the WHI, the control group, on the other hand, was given print materials explaining the “5-A-Day” dietary recommendations, which promoted five servings of fruits and vegetables daily.

Perhaps further echoing the issues within the dietary and lifestyle research world, the study was apparently funded by a challenge grant from a private philanthropist who strongly supported the study of diet and its role in cancer outcomes, since cancer survivors instead relied on “folklore, rumor, and hearsay.” Much like the WHI, opponents cried intervention bias before the study commenced, and this time around, counseling within the intervention group was intense and more frequent than the WHI, providing additional fuel to the opposition’s fire. The counseling was likely more intense to placate those supporters who felt that the WHI was unsuccessful due to its lack of extremeness regarding lowering dietary fat. Regardless of the opposition, the study set out across seven clinical sites within the US from 1995 to 2000. In total, it included 3088 women previously diagnosed and treated for early stage breast cancer.

About half of the study women were placed into the intervention group, receiving the intense lifestyle counseling. The efficacy of counseling was improved from the WHI: during the six years of the study adherence rates and dietary changes between the groups diverged significantly. The control group increased their fat intake by 13%, while the intervention group far exceeded expectations, increasing their average vegetable and fruit intake to 12 servings per day. Increased vegetable consumption was even confirmed through blood tests measuring carotenoids, the pigmented chemicals that give vegetables their color and accumulate in our blood after vegetable and fruit intake. Perhaps most important, weight changes were similar between the two groups, avoiding a major confounding factor. If the intervention group had lost more weight, this change could greatly skew data as overweight woman have a much higher risk of breast cancer recurrence, and weight loss can offset this risk and allow these women to live longer.8 Yet, much like the WHI, no difference was observed between the  groups after over seven years of follow-up. The rates of breast cancer recurrence, new breast cancer diagnosis, and death was similar.9

After the failures of the WHI and WHEL, the low-fat diet had one last attempt to win over the medical world. The last remaining of these massive studies was the Women’s Intervention Nutrition Study, known as WINS. Much like its contemporaries, WINS promoted a low-fat eating pattern. Furthermore, it continued to follow the stepwise increase in intensity of the intervention arms. WINS represented what may have been the last-ditch effort at a massive costly endeavor to prove the anticancer benefits of a low-fat diet. Women within the intervention arm found themselves bombarded with methods utilizing social cognitive theory, goal setting, modeling, self-monitoring (fat gram counting and recording), social support, and relapse prevention and management. Instead of simple telephone calls, women were individually counseled during eight hourly biweekly sessions followed by sessions every three months and optional monthly group sessions. Following in the footsteps of the WHEL study, it was emphasized that the point of the intervention was not to achieve weight loss, as this again could confound any benefits of the low-fat diet. Control subjects, on the other hand, received a single baseline dietician visit and were contacted by a dietician every third month afterwards. They also were given written information on general dietary guidelines, including information on vitamins and minerals.

Much like the WHEL study, the intense dietary intervention was effective, as these women decreased their fat intake by 19 grams per day at the five-year point, or about 9% of total calories. Despite the intensive intervention, fat decreases were similar to the WHI study. Unfortunately for the researchers, this time around women in the intervention group reduced their overall caloric consumption, providing worries that the intensity of the intervention was generating significant intervention bias. When interim analysis revealed that these women lost significantly more weight than the control group, these worries were confirmed.10 The interim analysis also revealed a hint at the intervention decreasing local recurrence, however, this suggestion was contested due to weight loss in the intervention arm, along with several other issues.11 While the authors did state that these results “could also be the result of chance,” in what seemed consistent with a culture of sugar-coating tangential results, they concluded that a “lifestyle intervention reducing dietary fat intake with modest body weight loss may improve the relapse-free survival of postmenopausal breast cancer patients.” In closing on the massively funded public studies, the WHI came full circle when long-term results were published in 2017, revealing that women within the intervention arm lost more weight that the control arm after 16 years of the study – a conclusion that was unsurprising given the massive amount of health interventions that these women experienced throughout the study. No difference was seen in deaths from breast cancer between the two groups.12 Women within the intervention arm did experience a slightly reduced risk of succumbing to their breast cancer, further touting the benefits of weight loss on breast cancer recurrence.

The Fat and Cancer Bias has Hurt Science

The medical world now has three costly and colossal studies testing the hypothesis that dietary fat is associated with breast cancer, and unfortunately, we are left with more questions than answers. Vegetable consumption was unfortunately consistently shackled to the low-fat diet, eliminating the possibility of assessing its effect on breast cancer diagnosis and recurrence. A low-fat diet seemed to have little or no effect on breast cancer occurrence and recurrence, consistent with Willett’s data and Doll’s concerns with his own data. Perhaps what these three massive studies signified – more so than all their medical findings combined – was the refusal to accept a lack of data supporting a benefit to lowering dietary fat to reduce the risk of breast cancer, that the anti-fat dominoes continue to fall in the opposite direction of the data, and this somehow has compelled its sentiment to linger throughout our hallowed medical institutions.

With the ability to analyze massive groups of individuals, their lifestyle habits, and their health status, came the ability to produce a continuous conveyor belt-like machine of studies linking foods and behaviors with heath and disease at a pace that quickly buried Armstrong and Doll’s data and initial warning. The WHI alone has produced almost 1,500 publications, a previously unheard-of number of reports. The reports range from lukewarm to evangelical in their demonization of certain foods and activities. They have even been criticized for the melodramatic tone, which was felt to elicit “shock, terror, and controversy.” Many follow-up studies from the WHI contradicted earlier reports, providing a “U-turn” and adding further fuel to contradictory media reports that left the public confused and often angry.13 Since that time, news sources reporting on the contradictory studies has now become commonplace, fueling an addiction to outrage, further enriched by the consistent production of inconsistent studies, leaving many individuals to throw their hands into the air and give up. The competing factors producing these recommendations helps to provide further insight to the inconsistent, and often absent dietary recommendations that we observed in Doll’s initial controversial study attempting to bring light to the root of the problem.14 Methods to prevent cancer, and studies to support these methods, remain perhaps the most inconsistent area within modern medicine.

Fat and Breast Cancer – The Recent Publication & Presentation:

Recalling that women in the intensive intervention group lost weight and decreased waist circumference, the authors of the WHI should be applauded for eliciting physical improvements from a plethora of lifestyle changes. However, the puck stops there. In 2018, the weight loss issue seemed all but forgotten as they published their manuscript Association of Low-Fat Dietary Pattern with Breast Cancer Overall Survival, revealing an improved 10-year survival in women in the intervention arm from 78 to 82%. However, was this surprising given the massive intervention and their weight loss?

The easy and obvious answer is no. Where things get dicey is when they attribute this to a low-fat dietary pattern (if you aren’t clear with the issue here, reread all the components of the intervention). It should be recognized that reduction in mortality is expected to be associated with these changes, especially weight loss and decreased central obesity. Isolating these benefits to an 8% reduction in total fat consumption, the plethora of other lifestyle changes, or the large inherent intervention bias present within the intensive intervention group is not possible.

Intervention bias is a common occurrence in similar studies and weight loss trials.15 For instance, the PREDIMED randomized trial revealed a significant reduction in breast cancer risk in the intervention arms, though minimal dietary changes occurred16

Labeling this benefit from a “low-fat dietary pattern” is misleading and speculative. No mechanisms were proposed regarding how a reduction in fat intake specifically would reduce the risk of death after breast cancer. The intervention group lost weight and waist circumference,12 violating the trial goal of assessing dietary changes and their impact on survival, not the impact of weight loss. It is well-established that weight loss can reduce risk of mortality, and android obesity is related to risk of metabolic syndrome and death. Along these lines, an increase in cardiovascular disease-specific survival was also seen, as would be expected with central and overall weight loss. Finally, vegetable consumption, regardless of fat or carbohydrate content, has been shown to be associated with lower breast cancer mortality.17

What conclusions can we make?

If you closely follow people and bombard them with a plethora of health changes, while constantly assessing whether they are following orders, they are likely to become healthier and lose weight. Which aspect of the intervention is responsible for this? It is impossible to say, but apparently you are more than free to take your pick. It may even be published in JAMA, headline your local paper, or give the mainstream media some new fodder for the evening news.

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Fat and Breast Cancer References:

    1. Chlebowski RT, Aragaki AK, Anderson GL, et al. Association of Low-Fat Dietary Pattern With Breast Cancer Overall Survival. JAMA Oncol. 2018;4(10):e181212. doi:10.1001/jamaoncol.2018.1212
    2. Howard B V., Van Horn L, Hsia J, et al. Low-Fat Dietary Pattern and Risk of Cardiovascular Disease. JAMA. 2006;295(6):655. doi:10.1001/jama.295.6.655
    3. Howard B V., Manson JE, Stefanick ML, et al. Low-Fat Dietary Pattern and Weight Change Over 7 Years. JAMA. 2006;295(1):39. doi:10.1001/jama.295.1.39
    4. Prentice RL, Caan B, Chlebowski RT, et al. Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer. JAMA. 2006;295(6):629. doi:10.1001/jama.295.6.629
    5. Beresford SAA, Johnson KC, Ritenbaugh C, et al. Low-Fat Dietary Pattern and Risk of Colorectal Cancer. JAMA. 2006;295(6):643. doi:10.1001/jama.295.6.643
    6. Lin J, Zhang SM, Cook NR, Lee I-M, Buring JE. Dietary Fat and Fatty Acids and Risk of Colorectal Cancer in Women. Am J Epidemiol. 2004;160(10):1011-1022. doi:10.1093/aje/kwh319
    7. Roth JA, Etzioni R, Waters TM, et al. Economic return from the Women’s Health Initiative estrogen plus progestin clinical trial: a modeling study. Ann Intern Med. 2014;160(9):594-602. doi:10.7326/M13-2348
    8. Champ CE, Volek JS, Siglin J, Jin L, Simone NL. Weight Gain, Metabolic Syndrome, and Breast Cancer Recurrence: Are Dietary Recommendations Supported by the Data? Int J Breast Cancer. 2012;2012:9. doi:10.1155/2012/506868
    9. Pierce JP, Natarajan L, Caan BJ, et al. Influence of a Diet Very High in Vegetables, Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer. JAMA J Am Med Assoc. 2007;298(3):289-298. doi:10.1001/jama.298.3.289
    10. Chlebowski RT, Blackburn GL, Thomson CA, et al. Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women’s Intervention Nutrition Study. J Natl Cancer Inst. 2006;98(24):1767-1776. doi:10.1093/jnci/djj494
    11. Thiébaut ACM, Schatzkin A, Ballard-Barbash R, Kipnis V. Dietary Fat and Breast Cancer: Contributions From a Survival Trial. JNCI J Natl Cancer Inst. 2006;98(24):1753-1755. doi:10.1093/jnci/djj504
    12. Chlebowski RT, Aragaki AK, Anderson GL, et al. Low-Fat Dietary Pattern and Breast Cancer Mortality in the Women’s Health Initiative Randomized Controlled Trial. J Clin Oncol. 2017;35(25):2919-2926. doi:10.1200/JCO.2016.72.0326
    13. Brown S. Shock, terror and controversy: how the media reacted to the Women’s Health Initiative. Climacteric. 2012;15(3):275-280. doi:10.3109/13697137.2012.660048
    14. Champ CE, Mishra M V, Showalter TN, Ohri N, Dicker AP, Simone NL. Dietary Recommendations During and After Cancer Treatment: Consistently Inconsistent? Nutr Cancer. 2013;65(3):430-439. doi:10.1080/01635581.2013.757629
    15. Ioannidis JPA. Biases in obesity research: Identify, correct, endorse, or abandon effort? Obesity. 2016;24(4):767-768. doi:10.1002/oby.21457
    16. Toledo E, Salas-Salvadó J, Donat-Vargas C, et al. Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial. JAMA Intern Med. 2015;175(11):1752. doi:10.1001/jamainternmed.2015.4838
    17. Thomson CA, Rock CL, Thompson PA, et al. Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women’s Healthy Eating and Living Study. Breast Cancer Res Treat. 2011;125(2):519-527. doi:10.1007/s10549-010-1014-9

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