Weight Gain Prior to Diagnosis and Survival from Breast Cancer

Over the past several decades, a large body of evidence has accumulated linking obesity with breast cancer incidence, and, to a lesser extent, survival, although the associations vary with menopausal status. For postmenopausal women, there is strong evidence for an increased risk of developing breast cancer and, once diagnosed, poorer survival in overweight or obese women (1, 2). This is mainly attributed to hormonal profiles that are higher in circulating levels of steroid hormones caused by increased adipose tissue conversion that may enhance tumor growth (3). In contrast, studies among premenopausal women have generally found modest inverse associations between body weight and breast cancer incidence (4, 5). This may be due to lower levels of bioavailable estrogens that are a result of anovulatory cycles, which can occur more frequently with obesity (6). However, there is some limited recent evidence that premenopausal women who are obese at diagnosis have decreased survival, which is similar to what has been observed among postmenopausal women (7-9).

Although a number of studies have shown that obesity at diagnosis decreases breast cancer survival (7-11), few studies have explored whether weight gain leading up to diagnosis can influence survival after a breast cancer diagnosis. Prior research has shown that prediagnostic adult weight gain is associated with risk of developing breast cancer (12) and increased mortality related to cardiovascular diseases, diabetes, and a number of primary cancers (13, 14). Adult weight gain reflects mainly increased accumulation of adipose tissue, and biological mechanisms hypothesized for the effects of weight gain on breast cancer prognosis include elevated levels of endogenous estrogens that are associated with conversion of androstenedione to estrogen in peripheral adipose tissue, lower circulating levels of sex hormone–binding globulin, hyperinsulinemia, and increased insulin-like growth factor-I levels (15). The identification of modifiable risk factors that can possibly reduce death after breast cancer diagnosis is of particular interest, as the number of women breast cancer survivors continues to rise globally.

Despite the growing number of studies that have looked at various body size indices at the time of breast cancer diagnosis, few studies have investigated how survival might be affected by changes in body size and weight over the life course. We investigated the effects of prediagnostic adult weight and weight change on mortality among women with breast cancer who participated in the population-based Long Island Breast Cancer Study Project (LIBCSP).

This study draws on data that were collected from participants as part of the LIBCSP, a case-control study of English-speaking residents of Nassau and Suffolk counties of Long Island, New York (16). LIBCSP participants were women newly diagnosed with a first, primary in situ, or invasive breast cancer between August 1, 1996, and July 31, 1997. Women were identified using a rapid reporting system established specifically for the LIBCSP and were confirmed by physician's and medical records. The attending physician was contacted to confirm study eligibility and to seek permission to contact the patient. Institutional review board approval of the study protocol was obtained from each collaborating institution and participating hospital and written informed consent was obtained from each participant before the interview. A total of 1,508 women with breast cancer, of which 1,273 had invasive breast cancer, participated in the case-control study interview. Vital status through the end of 2002 was determined through the National Death Index.

Baseline Data. The lifetime weight and most of the covariate data used in this analysis were collected as part of the LIBCSP baseline case-control interview. The main questionnaire was administered in-home by a trained interviewer and took ∼2 h to complete. Information obtained from the main questionnaire includes reproductive and menstrual history, exogenous hormone use, family history of cancer, physical activity, smoking history, alcohol intake, and demographic characteristics.⁷

As part of the baseline interview, participants reported height to the nearest inch and weight to the nearest pound at age 20 years and at 1 year before the date of breast cancer diagnosis. Weight at each relevant decade of life from age 20 years through age 70 years was also recorded.

Additionally, as part of the baseline case-control study, medical records were abstracted for tumor stage, estrogen receptor status, progesterone receptor status, and initial course of treatment. Nearly two thirds of baseline case interviews occurred before initiation of chemotherapy (16).

Follow-up Data. Follow-up information was obtained by trained interviewer via telephone from 1,098 case participants or their proxy in 2002 to 2004. There were 410 cases without follow-up interview data due to nonresponse, refusal, untraceability, or death without an identifiable proxy. Follow-up data used in this study were the covariates for tumor characteristics and treatment information.

As part of the LIBCSP follow-up, medical records were abstracted for 598 women. Trained abstractors reviewed medical records to determine each participant's tumor size and nodal status information for their initial breast cancer diagnosis. In addition, medical records were reviewed to determine the treatment regimen for each breast cancer case and these data were compared with the respondent's self-reported treatment regimen from the follow-up interview. A high concordance was found between information abstracted from records and self-reported radiation therapy (κ = 0.97), chemotherapy (κ = 0.96), and hormone therapy (κ = 0.92). Thus, for this study, the analysis is based on self-reported treatment at the baseline and follow-up interviews.

Study Outcome. For the LIBCSP follow-up study, the National Death Index was used to ascertain all-cause and breast cancer–specific mortality among study participants. Participants were followed from diagnosis until December 31, 2002, for a mean of 66.7 months (range, 2.7-88.6). Among the 1,508 women diagnosed with breast cancer, 198 (13.1%) deaths occurred. Based on International Classification of Diseases codes 174.9 and C-50.9 listed as a primary or secondary code on the death certificate, 128 (64.6%) deaths were due to breast cancer. There were nine additional cancer deaths arising in areas of common breast tumor metastases, including the brain and lung. Cardiovascular disease was the second most common cause of death, accounting for 21% of all deaths. For the assessment of breast cancer–specific death, we evaluated breast cancer listed in medical records as being the primary or underlying cause of death separately. Breast cancer as both the primary and underlying cause of death yielded similar results; therefore, we report only the results for breast cancer as the underlying cause of death.

Body Size Data. Body size variables include body mass index (BMI; kg/m²), height, and weight. Self-reported weight and height were examined for each relevant decade of life from ages 20 to 60 years, as well as the date 1 year before diagnosis (1). BMI was evaluated both as a continuous variable and categorized according to WHO guidelines (17). Because there were very few cases considered to be underweight (BMI <18.5) and including them in the reference group did not alter the results, three levels of BMI were used to categorize women: ideal weight (BMI <24.9), overweight (BMI 25-29.9), and obese (BMI ≥30).

Weight change variables were calculated for three time periods: from the 20s to 1 year before diagnosis date to approximate lifetime adult weight change for all women; from 20s to 50s to approximate weight changes during the premenopausal years among women who were postmenopausal at diagnosis; and from 50s to 1 year before diagnosis date to approximate postmenopausal changes in weight (1). We also evaluated change in weight for each relevant decade starting at age 20 years to detect patterns in timing of weight change that may influence breast cancer survival.

Menopausal Status. Menopausal status was derived using information provided on the baseline questionnaire (16). Postmenopausal status was defined as having a last menstrual period >6 months before the date of diagnosis or if she had both of her ovaries removed before the date of diagnosis. For women with unknown menopausal status, women were categorized as postmenopausal based on the 90th percentile for age at menopause in the control population, calculated according to smoking status. In this study, at the time of diagnosis, 1,006 women were categorized as postmenopausal and 472 were categorized as premenopausal.

For weight change analyses for the time periods from age 20 years to year before diagnosis, ages 20 to 50 years, and age 50 years to year before diagnosis, women were categorized as losing more than 3 kg, maintaining their weight (±3 kg for the time period; reference), and tertiles of weight gain over 3 kg. For evaluation of weight change by decade, categories were fixed to allow comparability across decades. For decade-specific analysis, women were categorized losing weight, maintaining their weight (no change in kg for the time period; reference), gaining 0.1 to 4.9 kg, and gaining ≥5 kg. For all weight change analyses, weight at the beginning of the interval was included in models to account for any residual confounding by starting body size. To reduce the possibility that weight change by decade associations we observed were due to the differences in sample size, additional analyses were conducted with the data set restricted to older women who had a reported weight measure at each time point. Restriction of the data set did not alter the results and therefore the results presented include all women.

Kaplan-Meier methods (18) were used to generate survival curves by body size and weight change (data not shown). Each body size and weight change variable of interest was evaluated to determine whether the proportional hazards assumption was met. No violation of this assumption was found. Cox proportional hazards regression (18) was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risk of all-cause and breast cancer–specific mortality. The results for overall and 5-year survival were similar; therefore, only overall survival is reported. Tests of trend were conducted using the continuous values for weight and BMI.

Effect measure modification on the multiplicative scale between categorical body size variables and other covariates was evaluated using the log likelihood ratio test to compare proportional hazards regression models with and without the cross-product terms (18). We evaluated models stratified by variables, which included exogenous hormone use (never used hormones, ever used hormones), menopausal status (premenopausal, postmenopausal), and family history of breast cancer in a first-degree relative (no family history, family history). Associations were also evaluated by stratification on the tumor characteristics estrogen receptor status (negative, positive), progesterone receptor status (negative, positive), tumor stage (in situ, invasive), nodal status (node-negative, node-positive), and tumor size (<2 cm, ≥2 cm).

All models were adjusted for age at diagnosis. Additional factors included in models as potential confounders included variables related to demographic factors (race, income, education, marital status), reproduction (parity, age at first live birth, breast feeding), and menstruation (age at menarche, age at menopause). Exogenous hormone use was also considered (hormonal birth control, hormone replacement) as was medical history (benign breast disease, family history of breast cancer), lifestyle factors (alcohol consumption, dietary fat and total caloric intake, cigarette smoking and physical activity), history of comorbidities reported at the baseline interview (high cholesterol, history of blood clots, diabetes, hypertension, previous myocardial infarction and stroke), tumor characteristics (tumor stage, tumor size and nodal status), and treatment undergone for the original breast cancer diagnosis.

For assessment of confounding, variables were included in multivariate models if they were related to either the exposure (BMI, weight change) or the outcome (death). Using backward elimination, potential confounders were removed from models beginning with those with the highest P value. Variables remained in the final models if their inclusion changed the estimate of effect by >10% (19). With the exception of age at diagnosis and history of hypertension, adjustment for most factors did not substantially alter the estimates of effect.

To further explore possible confounding by tumor characteristics, we conducted separate analyses restricted to women for whom we have complete tumor characteristic and tumor treatment data. There were no differences in effects or evidence of confounding by these variables for the relationship between BMI or weight change and mortality.

Because our results were found to vary modestly by menopausal status, and the relation between body size and breast cancer incidence varies substantially by menopausal status (20), all models were constructed for premenopausal and postmenopausal women separately. A total of 25 cases had missing data on menopausal status and were not included in analyses stratified by this factor.

Distributions of select characteristics by BMI category 1 year before diagnosis among women with breast cancer are shown in Table 1. Women who were obese 1 year before diagnosis had a higher proportion of breast cancer deaths than those who were not obese. Obese patients also tended to be older at time of diagnosis, and were more likely to be postmenopausal or have a family history of breast cancer. There was little difference in stage and estrogen receptor or progesterone receptor status in obese women compared with nonobese women.

Survival after breast cancer diagnosis among premenopausal and postmenopausal women by BMI group 1 year before diagnosis was evaluated using the Kaplan-Meier method. Premenopausal women who were obese 1 year before diagnosis had significantly lower survival than nonobese patients (P = 0.003; Fig. 1A). At 5 years after diagnosis, 83.6% of obese women were alive compared with 93.7% nonobese women. Using Cox proportional hazards models adjusted for age at diagnosis and history of hypertension, the HR for those who were obese compared with those considered of ideal weight 1 year before diagnosis was 2.85 (95% CI, 1.30-6.24) for breast cancer–specific death and 2.62 (95% CI, 1.26-5.45) for overall death (data not shown). The risk of breast cancer death increased by 7% for each unit increase in BMI (HR per kg/m², 1.07; 95% CI, 1.02-1.13). Similarly, weight at 1 year before diagnosis was associated with increased risk of death due breast cancer and overall causes among premenopausal women when comparing the highest (≥72.6 kg) versus lowest (<56.2 kg) quartile of weight (HR, 2.41; 95% CI, 0.91-6.39; HR, 2.27; 95% CI, 0.92-5.64, respectively; data not shown).

When comparing patients by BMI group among postmenopausal women, obese women did not have significantly different 5-year survival rates than nonobese women (92.9% and 94.5%, respectively; P = 0.12; Fig. 1B). However, obesity (BMI ≥30) 1 year before diagnosis was associated with an increase in breast cancer–specific mortality (HR, 1.88; 95% CI, 1.04-3.34) and for all-cause mortality (HR, 1.63; 95% CI, 1.08-2.45) when compared with ideal weight women.

Premenopausal Diagnosis. To examine whether prediagnostic weight gain during early adulthood might influence survival after a premenopausal breast cancer diagnosis, we evaluated the change in weight from age 20 years until 1 year before diagnosis with adjustments made for age at diagnosis, history of hypertension, and weight at age 20 years (Table 2). There was little effect for weight gain below 15.9 kg; however, gains of 15.9 kg or more increased risk of both breast cancer–specific and all-cause death over 2-fold, although the confidence intervals were wide.

Postmenopausal Diagnosis. Among women who were postmenopausal at diagnosis, lifetime, prediagnostic weight change during adulthood (defined as weight change age 20 years up to diagnosis) was associated with nearly a 2-fold increase in breast cancer–specific mortality (HR, 1.97; 95% CI, 0.74-5.27), with adjustments made for age at diagnosis, history of hypertension, and weight at age 20 years (Table 3). However, there was only limited evidence for a trend of increasing risk of mortality with increasing weight gain (P = 0.15). Elevated HRs were observed for women who lost >3 kg during this time period for both breast cancer–specific and all-cause death. Substantial weight gain after age 50 years, but before diagnosis, was associated with a near 3-fold increase in the HR for breast cancer–specific mortality for women who had a postmenopausal breast cancer diagnosis. For example, compared with women whose weight remained stable, those who had gain >12.7 kg after the age of 50 years had an increased risk of breast cancer death (HR, 2.95; 95% CI, 1.36-6.43) after adjustment for age at diagnosis, history of hypertension, and weight at age 50 years. Women who lost >3 kg during this time period also experienced an increased risk of breast cancer–specific and overall death (HR, 4.5; 95% CI, 2.0-10.2; HR, 2.8; 95% CI, 1.6-4.9, respectively).

Weight Change by Decade. Detailed analyses by decade of prediagnostic weight gain during the 10-year periods for ages 20 to 30 years, ages 30 to 40 years, or ages 40 to 50 years revealed no clear association for either all-cause or breast cancer–specific mortality among women with a premenopausal breast cancer diagnosis (data not shown). For postmenopausal women, analyses of weight change for 10-year periods between the ages of 20 and 50 years also showed little effect of weight change in the adult years until the age of 40 years (Table 4). However, there was an observed increased risk of overall and breast cancer death among postmenopausal women when comparing weight gain >5 kg between the ages of 40 and 50 years to those who did not gain weight (overall death HR, 2.69; 95% CI, 1.25-5.79; breast cancer death HR, 2.73; 95% CI, 0.89-8.43). This effect on breast cancer death was particularly strong among women who were considered of ideal weight (BMI <25) at age 40 years and who subsequently gained 5 kg or more in the following decade (HR, 5.42; 95% CI, 1.04-28.4), although interaction on the multiplicative scale was not statistically significant (P_interaction = 0.39).

We did additional analyses to explore whether the associations between weight, weight change, and breast cancer survival was modified by family history of breast cancer, level of physical activity, estrogen receptor status, progesterone receptor status, and use of exogenous hormones. The HR for the association between prediagnostic weight gain after the age of 50 years and all-cause mortality among postmenopausal women was elevated for both ever users and never-users of birth control, although the associations found in those who had used birth control were stronger (for weight gain >12.7 versus ± 3 kg; HR, 4.21; 95% CI, 1.08-16.5) than those found in women who reported never using birth control (HR, 2.24; 95% CI, 1.12-4.48); however, the interaction was not significant on the multiplicative scale. No material differences in the HR were observed for the other potential effect modifiers (data not shown).

In this population-based study of 1,508 with incident breast cancer with a median of 5.84 years of follow-up, we found that BMI at diagnosis and adult weight gain before diagnosis were associated with increased breast cancer–specific and overall mortality among both women who were premenopausal and postmenopausal at the time of diagnosis. Among women with a postmenopausal breast cancer diagnosis, we also found that high levels of weight gain during the perimenopausal and postmenopausal years were strongly associated with decreased survival after a breast cancer diagnosis. These associations remained unchanged when other prognostic factors were considered, such as age at diagnosis, tumor characteristics, treatment, and ever use of HRT for postmenopausal women.

There are several mechanisms thought to influence the adverse effects of high body weight on prognosis after a breast cancer diagnosis. The most widely accepted is the increased circulating sex hormones that are associated with excess adiposity and which have been shown to be related to breast cancer incidence (21). Increasing adiposity, particularly abdominal adipose tissue, is an important site of estrogen production in postmenopausal women, which is a result of conversion of androstenedione to estrone in peripheral adipose tissue. Furthermore, obesity has been related to lower sex hormone–binding globulin levels resulting in a higher fraction of free estrogen and testosterone, both of which have been shown to be positively correlated with body weight (22, 23).

Although few studies have examined the effect of prediagnostic body changes on subsequent survival after a breast cancer diagnosis, BMI and high body weight at diagnosis have been shown to have a negative influence on breast cancer prognosis in most reports (24). A review (24) identified 34 studies that had an obesity-related measure for breast cancer recurrence or death, of which 26 studies reported a positive association between obesity at diagnosis and recurrence or survival. We found that a high BMI and body weight at the time of diagnosis was associated with over a 2-fold increase in mortality among women who were premenopausal at the time of breast cancer diagnosis. Our results are similar to those found in two previous studies that have observed a stronger association between mortality and obesity among women who were premenopausal at the time of their breast cancer diagnosis than those who were postmenopausal (8, 25).

Few studies have evaluated whether weight change over the life course affects prognosis after breast cancer diagnosis. Our results for prediagnostic weight and weight gain over the adult life course are compatible to another study that also investigated adult weight gain on breast cancer survival. Huang et al. (10) found a strong increased risk of death due to breast cancer for weight gain of 20 kg or more since the age of 18 years, showing increased RR of 2.44 (95% CI, 1.40-4.25). However, another recent study found no association with breast cancer mortality for weight gain over 31 pounds after age 18 years (HR, 1.02; 95% CI, 0.82-1.27; ref. 26). It is uncertain why these results would differ, although it may be due to the inconsistency of definitions used in these two studies for weight gain and differing reference groups, both studies including women who lost weight. In our study, we found that women who had lost 3 kg or more since age 20 years had increased mortality when compared with those who had maintained their weight within 3 kg. It is unclear why postmenopausal women who lost weight experienced an increase in mortality, although Ewertz et al. (27) found similar results, reporting that weight loss >5 kg in the 10 years before breast cancer diagnosis was associated with a 60% increased risk of death due to all causes. One possible explanation for the higher number of deaths among those who lost weight may be due to cancer-related morbidity in the years leading up to diagnosis and may be an indicator for disease progression that would inherently increase risk of mortality (28). There is also evidence that intentional weight loss can affect immune function in postmenopausal women (29). We were not able to assess the association for weight gain among women who were obese at age 20 years compared with those who were not obese due to the small numbers of women who were obese at age 20 years.

The timing of prediagnostic weight gain may be an important factor in survival after a breast cancer diagnosis. Perimenopausal weight gain has been hypothesized to be particularly deleterious to breast cancer survival due to the changing hormonal milieu at this time (30). The 2-fold increase in the HR for breast cancer mortality among postmenopausal women seen in our analysis for weight gain in the years leading up to menopause, from age 40 to 50 years, is consistent with this hypothesis. The increased risk of death was particularly strong for women who started out with ideal weight (BMI <25) at age 40 years and subsequently gained a large amount of weight in the following decade, whereas for women with a BMI ≥25 and who had gained large amounts of weight we did not see any difference in mortality. Most postmenopausal breast tumors have been subject to a long promotion and initiation period and are therefore not likely to be detected until many years after these events occur. Weight gain during this time, in particular, the abdominal disposition seen with adult weight gain, could contribute to tumor promotion through alterations in hormonal and metabolic characteristics including high levels of estrogens. Therefore, precursor lesions that are exposed to promoting agents in the perimenopausal years could further enhance the development of detectable neoplasms.

We found that both prediagnostic BMI and weight gain after the age of 50 years influenced survival among postmenopausal women. These two measures are related and were modestly correlated in this study (r = 0.6). After mutual adjustment for both BMI and weight gain, the associations remained for weight gain after age 50 years, although they were somewhat attenuated for BMI. These results are consistent with the idea that adult weight gain reflects an increase in central adiposity, which is thought to be more important in determining circulating hormone levels than total body fat mass and subsequently a better predictor of breast cancer survival than BMI alone (31). However, other studies have shown BMI to be a stronger predictor of breast cancer survival (22). Further studies on both BMI and weight gain are warranted to confirm our findings and to gain a better understanding of how these measures affect breast cancer survival.

The adverse effects of excess adiposity on breast cancer mortality in postmenopausal women has been attributed to high circulating estrogen levels, and survival has been shown to be reduced in those with estrogen receptor–positive tumors (31). In our analyses, however, BMI remained an important predictor of breast cancer survival after adjustment for tumor receptor status, suggesting that other biological influences may be responsible for the effect of BMI on breast cancer prognosis. In addition to increased levels of sex hormones, obesity is also related to other hormonal and metabolic conditions that may affect breast cancer incidence and survival. Overweight is associated with hyperinsulinemia (32) and increased levels of insulin-like growth factor-I levels, which have been shown to be important mitogens and growth regulators in mammary cells (33) and have been linked to breast cancer occurrence, particularly among premenopausal women (34).

Our finding that BMI was a stronger predictor of breast cancer survival in premenopausal women than that seen in postmenopausal women is interesting given that BMI is inversely related to breast cancer development in premenopausal women. The relationship of BMI with breast cancer survival has often been attributed to differences in tumor characteristics at diagnosis (35). However, we found little difference in the relationship between BMI and tumor characteristics when comparing premenopausal and postmenopausal women, although we did find that estrogen receptor–positive tumors were more slightly more frequently found in obese premenopausal women than obese postmenopausal women. It is possible that this slight discrepancy in estrogen receptor positivity may account for some of the excess mortality seen in obese premenopausal women, although in our study the effect of high BMI on decreased breast cancer survival was independent of estrogen receptor and progesterone receptor status.

It is unclear whether our lack of information on weight changes after diagnosis could have strongly affected our results. Only a few studies have addressed weight change after breast cancer diagnosis, and results have been inconsistent (25, 36-38). Whereas the Nurses' Health Study (n = 5,204) reported an increased risk of breast cancer death with increasing weight gain after breast cancer diagnosis (25), other studies have failed to find an association between postdiagnostic weight gain and prognosis (38, 39). Thus, it is not clear whether weight gain after diagnosis influences mortality.

The use of self-reported body size measures is also a potential concern in this study. Other studies, however, have shown good correlation between self-reported weight and measured weight among women (10, 40). One cross-sectional study conducted to determine the accuracy of self-reported heights and weights among women ages 40 to 81 years compared values obtained through mailed questionnaires to those ascertained by a trained technician (40). The authors report age-adjusted Pearson correlations between technician measurements and self-measurements to be 0.99 for weight. Also, recalled weight for several years prior has been shown to be highly correlated with actual measurements that had been recorded on school physical examination forms (r = 0.87) in the Nurses' Health Study (10). Our use of weight at 1 year before diagnosis to avoid some residual disease affecting weight at diagnosis relies on recalled weight, whereas weight at diagnosis used current weight. However, it is reassuring that our results did not differ when using reported weight at interview or reported weight 1 year before diagnosis.

In summary, our study findings show that prediagnostic adiposity has an effect on breast cancer survival, where high BMI and substantial weight gain have a strong negative effect on prognosis after a breast cancer diagnosis. Obesity and weight gain in adulthood are modifiable risk factors for breast cancer occurrence and survival and our results show the importance of weight management, particularly during the perimenopausal and postmenopausal years in the prevention of excess mortality after menopause.

We thank the following for their valuable contributions to the LIBCSP: members of the Long Island Breast Cancer Network; the 31 participating institutions on Long Island and in New York City, New York; our NIH collaborators, Gwen Colman, Ph.D., National Institutes of Environmental Health Sciences; G. Iris Obrams, M.D., Ph.D., formerly of the National Cancer Institute; members of the External Advisory Committee to the population-based, case-control study: Leslie Bernstein, Ph.D. (Committee chair), Gerald Akland, M.S., Barbara Balaban, MSW, Blake Cady, M.D., Dale Sandler, Ph.D., Roy Shore, Ph.D., and Gerald Wogan, Ph.D.; as well as other collaborators who assisted with various aspects of our data collection efforts including Regina M. Santella, Ph.D., Mary S. Wolff, Ph.D., Steven Stellman, Ph.D., Maureen Hatch, Ph.D., Gail Garbowski, MPH, Geoff Kabat, Ph.D., H. Leon Bradlow, Ph.D., David Camann, B.S., Martin Trent, B.S., Jan Beyea, Ph.D., Ruby Senie, Ph.D., Carla Maffeo, Ph.D., Pat Montalvan, Gertrud Berkowitz, Ph.D., Margaret Kemeny, M.D., Mark Citron, M.D., Freya Schnabel, M.D., Allen Schuss, M.D., Steven Hajdu, M.D., and Vincent Vinceguerra, M.D.