Editor's Note: Breast cancer patients may experience overweight or obesity during treatment due to medication side effects and hormonal fluctuations. What impact does being overweight or obese have on patient prognosis? At the recent San Antonio Breast Cancer Symposium (SABCS), numerous new research findings, clinical practices, and treatment advancements were presented. One study from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) analyzed the relationship between overweight/obesity and prognosis in early-stage breast cancer patients. Oncology Frontier invited Dr. Cuizhi Geng from The Fourth Hospital of Hebei Medical University to summarize this relationship and share clinical intervention strategies.

Oncology Frontier: Could you briefly introduce this study and share your perspective on the relationship between overweight/obesity and prognosis in early-stage breast cancer?

Dr. Cuizhi Geng:This study holds significant clinical value. At the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) database analysis showed that for ER-positive premenopausal/perimenopausal breast cancer patients, obesity (BMI ≥30 kg/m²) was strongly and independently associated with increased mortality risk (P < 0.00001) compared to patients with lower body weight. However, obesity had little impact on the prognosis of ER-negative or postmenopausal ER-positive breast cancer patients. Although this relationship was acknowledged, it was also believed that the data might be influenced by various confounding factors.

In response, the EBCTCG conducted a re-analysis in 2024. This study included 147 clinical trials from the EBCTCG database, covering nearly 207,000 patients over a span of nearly 40 years. These patients underwent BMI measurements within two years of their breast cancer diagnosis, with BMI ranging from 15 to 50 kg/m². Comprehensive data were collected on patient age, menopausal status, tumor size, lymph node metastasis, ER status, and HER2 status. Cox regression analysis was used to assess the relationship between BMI and the risk of distant recurrence and breast cancer-related mortality. The study also evaluated the relative risk increase for every 5 kg/m² rise in BMI and compared the risks of distant metastasis and death across three BMI categories:

• Obese group: BMI 30–50 kg/m², average BMI 34.7 kg/m²
• Overweight group: BMI 25–30 kg/m², average BMI 27.3 kg/m²
• Lean group: BMI 15–25 kg/m², average BMI 22.2 kg/m²

The study revealed five key findings:

1. Overall Population: For the entire study population, each 5 kg/m² increase in BMI was associated with a 6% increase in the relative risk of first distant metastasis (RR 1.06, P < 0.0001).
2. Group Comparison: Compared to the lean group, the overweight group had a 7% higher risk of first distant metastasis (RR 1.07, P < 0.0001), while the obese group had a 17% higher risk (RR 1.17, P < 0.0001), both of which are clinically significant.
3. Menopausal Status: Among premenopausal women, each 5 kg/m² increase in BMI raised the risk of distant metastasis by 8% (RR 1.08, P < 0.0001). In postmenopausal women, this increase was 5% (RR 1.05, P < 0.0001).
4. ER Status: There was little difference between ER-positive and ER-negative groups. For both groups, each 5 kg/m² BMI increase resulted in a 6% increase in distant metastasis risk (RR 1.06).
5. Mortality: The correlation between BMI and breast cancer mortality was consistent with that between BMI and distant recurrence.

Two main conclusions can be drawn from these findings:

• First, in all types of early-stage breast cancer patients, being overweight or obese is associated with an increased risk of distant recurrence and breast cancer mortality. This highlights the need to address weight management in clinical practice, especially regarding the relationship between weight and tumor metastasis or death.
• Second, the relative risk increase for every 5 kg/m² rise in BMI is modest and may be influenced by confounding factors. Additionally, due to the 40-year span and complexity of the patient data, these results should be interpreted cautiously and require further validation through prospective studies.

This study also raises an important clinical question: If overweight and obesity are linked to increased breast cancer recurrence and mortality, should clinicians implement weight-loss interventions? For example, glucagon-like peptide-1 (GLP-1) receptor agonists, commonly used for diabetes management, could also help with weight loss by slowing gastrointestinal motility and reducing appetite.

Oncology Frontier: The study indicates differences in how overweight and obesity impact prognosis in premenopausal and postmenopausal women. What might explain this difference, and how should these two groups be managed differently in clinical practice?

Dr. Cuizhi Geng: I would like to offer some insights to encourage further thought. I believe that in premenopausal women, continuous weight gain and obesity after breast cancer diagnosis are largely due to endocrine disorders. It is well known that most premenopausal patients receive ovarian function suppression (OFS) therapy, pushing them into a perimenopausal state. This can cause hormonal imbalances, mainly reflected in estrogen metabolism disorders or decreased estrogen levels compared to pre-treatment.

Additionally, patients treated with tamoxifen, even without OFS, experience disrupted hormone balance, leading to fat accumulation, especially around the abdomen, resulting in noticeable weight gain. Many patients report feeling heavier after taking these medications.

Another factor is the special role premenopausal women play within their families. Observational data from clinics suggest that after surgery, family members pay extra attention to patients’ nutrition, which can also contribute to weight gain.

It is well known that increased fat leads to higher estrogen levels, as adipose tissue is a key source of estrogen. During perimenopause and postmenopause, hormonal changes contribute to weight gain, which in turn raises estrogen levels, creating a cycle. Estrogen levels are closely linked to the prognosis of ER-positive patients. For those with high ER receptor levels, excess estrogen binding to these receptors can make tumor recurrence more difficult to prevent. Conversely, lowering estrogen levels may reduce or even eliminate tumors. However, this theoretical relationship still requires further clinical research for confirmation.

Oncology Frontier: The study recommends incorporating weight loss interventions for overweight or obese early-stage breast cancer women into adjuvant therapy trials. What are your thoughts on this? How can the effectiveness and feasibility of these interventions be ensured in practice?

Dr. Cuizhi Geng: Although there is a lack of prospective studies, the detailed clinical data mentioned above still provide valuable insights for clinicians in the breast cancer field. It reminds us to pay close attention to weight management in ER-positive early-stage breast cancer patients after treatment. While it is possible to consider adding weight loss medications, such as semaglutide, in adjuvant therapy, I believe this is neither a long-term nor practical solution. Semaglutide requires long-term use, and discontinuation could lead to weight regain. Therefore, for these patients, medication should not be the primary focus, and alternative solutions should be explored.

Based on years of clinical experience, we have found that one of the most effective weight loss methods during or after breast cancer surgery and endocrine therapy is physical exercise. In our routine patient education, we consistently advise patients to engage in more than 30 minutes of daily exercise. The intensity should be enough to induce light sweating and elevate the heart rate to over 120 beats per minute, which qualifies as effective exercise. This not only boosts the immune system but also helps burn excess body energy. We always emphasize that illness is not to be feared; enhancing immunity cannot rely solely on medication and requires consistent physical activity. For breast cancer patients, we recommend exercises such as yoga, swimming, brisk walking, Tai Chi, Tai Chi sword, and Baduanjin, all of which can provide significant benefits.

Secondly, weight loss also requires adjustments in dietary structure. With the progress of urbanization and improved living standards, the intake of high-calorie and high-sugar foods has increased, leading to a growing proportion of overweight and obese individuals. Postoperative breast cancer patients often believe they need to increase nutrition to aid recovery, but I think their diet should be adjusted. This includes consuming high-quality proteins like milk, eggs, shrimp, and fish. Additionally, a low-fat diet should be followed, reducing the intake of fatty meats, especially pork fat. It’s also important to increase the consumption of vegetables and fruits.

Of course, with aging, the decline in estrogen levels can lead to earlier and more severe osteoporosis, so patients should consider taking calcium supplements and getting appropriate sun exposure depending on weather conditions. I believe that combining a balanced diet with exercise is the best approach to weight loss.

Thirdly, it’s necessary to improve patients’ awareness so they understand that weight management is closely related to their diet. Nowadays, many people lead sedentary lifestyles. Even if their calorie intake remains unchanged, aging and decreased physical activity mean they need to reduce their food intake by 10% to 20% over time. Of course, this adjustment requires a gradual process. At this stage, I personally do not strongly support using medication for weight loss during adjuvant therapy. Instead, I advocate for addressing this issue through exercise, dietary adjustments, and reduced caloric intake.

Dr. Cuizhi Geng

• Distinguished Professor and Doctoral Supervisor
• Breast Center, Fourth Hospital of Hebei Medical University
• Council Member, Chinese Anti-Cancer Association
• Council Member, Chinese Society of Clinical Oncology (CSCO)
• Vice Chair, Breast Cancer Expert Committee, CSCO
• Vice Chair, Clinical Oncology Branch, Chinese Women Physicians Association
• Standing Member, Tumor Clinical Research Management Committee, Chinese Anti-Cancer Association
• Member, Breast Cancer Committee, Chinese Anti-Cancer Association
• Chair, Breast Cancer Committee, Hebei Anti-Cancer Association