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Adult Weight Gain Increases Risk of All Types of Breast Cancer
American Cancer Society study finds weight gained in adulthood increases risk of all types, stages and grades of breast cancer.
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Reporting Source: "Obesity Raises Breast Cancer Risk." FoxNews.com, May 22, 2006.
Primary Source : "Adult Weight Gain and Histopathologic Characteristics of Breast Cancer among Postmenopausal Women." Cancer, July 1, 2006; 107:.

Expert Comments by Sue Hankinson, MPH, ScD
Associate Professor
Department of Epidemiology, Harvard School of Public Health
Associate Professor
Department of Medicine, Harvard Medical School, Boston, MA

BREASTLINK ANALYSIS
By Mary Batten

This is the first study to investigate the relationship between adult weight gain and type of breast cancer. One of the study's strengths is its large numbers - some 44,000 postmenopausal women drawn from the American Cancer Society's Cancer Prevention Study II Nutrition Cohort. Lead researcher Heather Spencer Feigelson, PhD, MPH, and colleagues at the American Society retrospectively examined the types of breast cancer that occurred among these women, none of whom used hormone replacement therapy (HRT). By looking only at non-HRT users, the researchers were able to eliminate this confounding factor of hormone therapy, which is already well known to be associated with an increased risk of breast cancer.

The finding that excess body weight significantly increases risk of all kinds of breast cancer adds more support for the importance of controlling body weight and avoiding obesity. Weight is one of the few breast cancer risk factors that women can control.

Background
There is a lot of evidence that obesity increases risk of postmenopausal breast cancer (Ref. 2). The mechanism by which this happens is believed to be the increase in estrogen production that occurs in fat cells (Refs. 3-4). After menopause, when the ovaries have stopped producing estrogen, small amounts of this hormone continue to be produced in the body. Hormones called androgens (androstenedione and testosterone) that are produced in the adrenal glands, fatty tissues, and certain normal breast cells are converted into estrogen by the enzyme aromatase. The more excess weight a woman has, the more estrogen is being produced. Several previous studies have looked at weight gain in relation to hormone receptor status (Refs. 5-7) but few have investigated the association between excess weight and tumor stage, grade, or histologic type.

Use of postmenopausal hormone therapy affects the relationship between obesity and breast cancer (Refs. 2, 8-9). In an earlier study, these same researchers found that obesity was strongly associated with increased risk of breast cancer only among women who were not using postmenopausal hormone therapy (Ref. 9). In that same study, they also found that weight gained after age 18 was a stronger predictor of breast cancer risk than body mass index (BMI). This study takes the research a step further to examine whether there is a relationship between adult weight gain and cancer type, grade, and stage.

The Study
What Was Being Studied?
The relation between several histopathologic characteristics of invasive breast cancer and adult weight gain among postmenopausal women who were not using postmenopausal hormone therapy.

How Was Information Gathered?
This was a prospective study based on a group of 44,161 postmenopausal women enrolled in the American Cancer Society's Cancer Prevention Study (CPS) II Nutrition Cohort. This cohort is a sub-group of some 1.2 million participants in CPS-II, a prospective study of cancer mortality that was established in 1982. Beginning in 1997, the participants completed questionnaires every two years. Among the items reported were newly diagnosed cancers, menopausal status, and weight gain. Only women who were not current users of hormone therapy were eligible for this study.

The authors used patient medical records and state cancer registries to verify cases of breast cancer diagnosed between 1992 and August 31, 2001. The analysis was limited to invasive breast cancer.

Medical records were used to collect information about the following tumor characteristics: histologic type, stage, grade (1,2,3), and ER/PR status. A pathologist examined reviewed a subset of the records to assess coding accuracy. Total weight gain change was calculated from the women's reported weight at age 18 years and the current weight on each questionnaire. Weight gain categories were defined as 21 to 40 pounds, 41 to 60 pounds, and more than 60 pounds gained since age 18.

Results
A total of 1200 cases of breast cancer developed among the 44,161 postmenopausal women who were not taking hormone therapy during the study period. The greater the adult weight gain, the greater the risk for all histological types, tumor stages, and grades of breast cancer, particularly advanced cancers. Compared to women who gained 20 pounds or less during adulthood, women who gained more than 60 pounds were almost twice as likely to have ductal type tumors and more than 1.5 times more likely to have lobular type cancers. The most obese women -- those who gained more than 60 pounds -- were up to three times more likely to have regional or distant metastases than women with less weight gain. Not surprisingly, weight gain increased risk of ER-positive/PR-positive tumors but not ER-negative/PR-negative tumors.

The researchers conclude: "These data further illustrate the relation between adult weight gain and breast cancer and the importance of maintaining a healthy body weight throughout adulthood" (Ref. 1).

EXPERT COMMENTS
By Sue Hankinson, MPH, ScD
Associate Professor, Department of Epidemiology, Harvard School of Public Health
Associate Professor, Department of Medicine, Harvard Medical School
181 Longwood Avenue
Boston, MA 02115
Phone: 617-525-2751
e-mail: sue.hankinson@channing.harvard.edu

This was a large prospective study that was very nicely designed. The researchers did a very careful data analysis and really added some new information to our understanding of the relationship between obesity and breast cancer risk in postmenopausal women.

It has been known for a number of years that adult weight gain increases the risk of breast cancer in postmenopausal women. Weight is one of the few lifestyle factors that women can control to decrease their risk. What is new about this study is that it looks at the relationship between weight gain and breast cancer risk more carefully by examining the characteristics of the tumor itself -- histology, ductal versus lobular subtypes, estrogen receptor status, and stage at diagnosis.

The results were generally what I would predict based on what I know about the biology of the different breast cancer subtypes. But sometimes in science you do not see what you expect, so it's always nice to see these associations empirically.

With respect to the mechanism that's involved, there's a consensus that the production of estrogen in fatty tissue is probably the primary mechanism. However, there are other possible mechanisms that may also be playing a role such as hyperinsulinemia.

You see the relationship between weight gain and breast cancer more clearly among women that are not taking this additional big bolus of hormones in hormone replacement therapy. That's why the researchers only followed women who were not using postmenopausal hormones. Taking postmenopausal hormones tends to mask the association between obesity and breast cancer because hormone users are already increasing their risk (and very likely through the same mechanism as obesity) by taking the drugs.

One of the next big questions is whether adult women will decrease their risk of breast cancer if they lose weight. We think this will be the case but there are very few studies that have specifically looked at that. If women that are postmenopausal start an exercise program, if they lose weight, will they reap benefit in terms of later breast cancer risk? Probably yes, but confirmation is needed.

The message for everyone is manage your weight well. Maintain, lose, or, at least, don't gain, as appropriate for whatever weight a woman is because it's so hard to take it off. This study deals only with breast cancer but maintaining a healthful weight applies to many other diseases as well.


REFERENCES
Bibliography
1. Feigelson HS, Patel AV, Teras LR, et al. "Adult Weight Gain and Histopathologic Characteristics of Breast Cancer among Postmenopausal Women." Cancer, July 1, 2006; 107.
2. IARC. IARC Handbooks of Cancer Prevention: Weight Control and Physical Activity.. Lyon: IARC Press, 2002.
3. Hankinson SE, Willett WC, Manson JE, et al. "Alcohol, Height, and Adiposity in Relation to Estrogen and Prolactin Levels in Postmenopausal Women." Journal of the National Cancer Institute 1995; 87:1297-1302.
4. Potischman N, Swanson C, Siiteri P, Hoover R. "Reversal of Relation between Body Mass and Endogenous Estrogen Concentrations with Menopausal Status." Journal of the National Cancer Institute 1996; 88:756-758.
5. Cotterchio M, Kreiger N, Theis B, et al. "Hormonal Factors and the Risk of Breast Cancer according to Estrogen- and Progesterone-Receptor Subgroup." Cancer Epidemiology Biomarkers and Prevention 2003; 12:1053-1060.
6. Enger SM, Ross RK, Paganini-Hill A, et al. "Body Size, Physical Activity, and Breast Cancer Hormone Receptor Status: Results from Two Casse-Control Studies." Cancer Epidemiology Biomarkers and Prevention 2000; 9:681-687.
7. Colditz GA, Rosner BA, Chen WY, et al. "Risk Factors for Breast Cancer According to Estrogen and Progesterone Receptor Status." Journal of the National Cancer Institute 2004; 96:218-228.
8. Huang Z, Hankinson S, Colditz G, et al. "Dual Effects of Weight and Weight Gain on Breast Cancer Risk." JAMA 1997; 278:1407-1411.
9. Feigelson H, Jonas C, Teras L, et al. "Weight Gain, Body Mass Index, Hormone Replacement Therapy, and Postmenopausal Breast Cancer in a Large Prospective Study." Cancer Epidemiology Biomarkers and Prevention 2004; 13:220-224.

Internet Sources
Obesity Linked to All Types of Breast Cancer
American Cancer Society, May 22, 2006
http://www.cancer.org/docroot/MED/content/MED_2_1x_Obesity_Linked_To_All_Types_of_Breast_Cancer.asp?sitearea=MED

Obesity, Estrogen Linked to Breast Cancer
WebMD.com, Aug. 19, 2003
http://www.webmd.com/content/article/72/81799.htm

Obesity Increases Breast Cancer Risk
WebMD.com, May 17, 2004
http://www.webmd.com/content/article/87/99433.htm

Striking a Healthy Energy Balance
National Cancer Institute, Jan. 30, 2004
http://www.cancer.gov/newscenter/benchmarks-vol4-issue1/page1

Breast Cancer Rates on the Rise among Asian Americans
American Cancer Society, Aug. 1, 2002
http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Breast_Cancer_Rates_On_The_Rise_Among_Asian_Americans.asp

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