Obese women have increased risk of breast cancer and worse outcomes than normal weight women. Being overweight during childhood is protective against breast cancer in adulthood as long as weight gain does not continue during adulthood. Obese women are most likely to develop hormone receptor positive (ER+/PR+) disease.
This subtype appears to be especially vulnerable to the harmful effects of obesity on prognosis. The effects of systemic treatment appear to be lost more rapidly in obese breast cancer patients.
Being overweight at young age does not increase risk
While tall girls have heightened breast cancer risk in adulthood, overweight girls do not. In fact, generally speaking, being overweight appears to be protective against breast cancer until perimenopause, for reasons that are not well understood.
However, even though overweight and obese women have a lower risk of premenopausal breast cancer, obesity appears to contribute to more aggressive forms of breast cancer with unfavorable prognosis when younger women do develop the disease. One study reported that being overweight at age 18 was associated with increased breast cancer-specific mortality in premenopausal women who developed estrogen receptor negative (ER-) breast cancer.
Weight gain during adulthood increases breast cancer risk
Women who gain weight during adulthood have increased breast cancer risk after menopause whereas women who lose it reduce their risk. Weight gain is a plausible risk factor since some factors involved in the process of gaining weight (such as excess insulin and inflammation) also promote breast cancer development and growth.
Postmenopausal breast cancer risk increases steadily as body mass index (BMI) increases irrespective of BMI at age 20. One study reported that women whose BMI increased more than 5 kg/m2 between age 20 and baseline age had almost twice the postmenopausal breast cancer risk as the women with no change or a loss in BMI. (For a woman of height 5'4“ an increase of 5 kg/m2 is equivalent to gaining approximately 30 pounds.) In fact, gaining weight over time increases the risk of breast cancer compared to maintaining a high, but relatively stable, BMI.
On the other hand, one study reported that compared to women whose weight changed less than 5% during the two years prior to diagnosis, women who lost more than 5% of their weight had 2.9 times the risk of death from breast cancer. The group of women who lose weight before a breast cancer diagnosis includes those whose weight loss is tied to undetected metastasis of their disease.
Obesity may be linked to disease aggressiveness
Obese premenopausal women tend to be diagnosed with more aggressive disease than obese postmenopausal women. Evidence exists that while obesity does not appear to increase risk of premenopausal breast cancer, when such cancer does develop, it has an aggressive profile. There is conflicting evidence as to whether obesity increases the risk of triple negative or HER2 overexpressing (HER2+) subtypes in premenopausal women. However, obese premenopausal women tend to have larger tumors with higher tumor grade and stage than similar normal weight women.
Adult weight gain is associated primarily with increased risk of ER+/PR+ breast cancer after menopause. However, risk for ER-/PR- tumors among postmenopausal women also has been reported to be increased as a result of weight gain.
Obesity at diagnosis worsens prognosis
Obesity at diagnosis of early stage breast cancer worsens prognosis whether a woman develops breast cancer before or after menopause. (Underweight (BMI < 18.5 kg/m2) women also have worse survival.) Obesity appears to contribute to worse outcomes through factors associated with excess weight, such as higher blood insulin, glucose and estrogen levels, as well as inflammation, and growth factors secreted by fat cells. One study reported that obesity is not a risk factor for breast cancer in women who are not insulin resistant. However, there is also some evidence that fat tissue itself can directly promote cancer by providing a favorable environment for tumor growth.
Obese women have been shown to have a less favorable outlook than normal weight women since higher BMI is associated with increasing tumor size, grade, and stage. Having said this, some women are more vulnerable to unfavorable effects of obesity than others, even taking account tumor size, grade and stage. Several studies have concluded that obesity is most strongly associated with inferior disease free survival and overall survival in women with ER+ disease.
Weight loss surgery (bariatric surgery) has been shown to reduce aromatase expression, estrogen availability and estrogen receptor activity in premenopausal women without breast cancer. Weight loss surgery after diagnosis is associated with reduced risk of recurrence among obese breast cancer survivors compared to similar women who do not undergo bariatric surgery. However, the benefits appear to apply to triple negative as well as estrogen receptor positive breast cancer. A 2023 study using a mouse model of obesity-driven triple negative breast cancer demonstrated that vertical sleeve gastrectomy combined with a low-fat diet suppressed tumor growth compared to continued obesity. However, notably, calorie restriction without bariatric surgery was found to be even more effective in counteracting obesity’s cancer-promoting effects.
Part of the explanation for the poor prognosis of obese breast cancer patients is the prevalence of type 2 diabetes. Recurrence-free survival and overall survival are significantly worse in diabetic compared to non-diabetic patients, even after adjusting for BMI. The combination of obesity and diabetes results in risk of recurrence that is higher than for obesity or diabetes alone.
Most studies that investigate breast cancer survival examine only the first five years after diagnosis when the prognosis of ER+ disease is more favorable than triple negative and other aggressive forms of breast cancer. However, longer term studies have consistently shown that the risk of recurrence of aggressive disease is actually lower after five years than the risk for ER+/PR+ disease. Long-term survival of women obese at diagnosis have been shown to be inferior to than of non-obese women. One study reported that the risk of dying from breast cancer remained elevated for patients with high BMI throughout 30 years of observation. This is partly because systemic treatment appears to loose its effect more rapidly in obese patients.
Obesity also predicts worse outcomes in HER2+ patients. The production of leptin, a hormone secreted primarily by fat cells, is enhanced in obesity. Leptin has also been shown to promote breast cancer cell growth and impair response to Herceptin, which is used to treat HER2+ disease. One 2020 study reported that overweight or obese women with ER+/PR+/HER2+ disease were less likely to achieve pathologic complete response after neoadjuvant treatment. Another study reported that among relapsed HER2+ patients, overall survival and time to progression decreased with increasing BMI: the median overall survival for normal weight patients was 40 months, whereas it was 36.5 months for overweight and 31 months for obese patients.
Obese women have less favorable response to systemic treatments
Obese women might be less likely to respond favorably to chemotherapy, aromatase inhibitor, and tamoxifen treatment, although not all studies are in agreement. One study reported that the presence of fat cells promoted resistance to Adriamycin chemotherapy in a wide variety of human and mouse breast cancer cells.
The effects of systemic treatment appear to be lost more rapidly in obese breast cancer patients. Both chemotherapy and endocrine therapy (including aromatase inhibitors and tamoxifen) appear to be less effective after 10 or more years for women with BMIs over 30 kg/m(2).
Merely being overweight does not worsen breast cancer prognosis
However, being merely overweight at diagnosis does not appear to worsen prognosis. Several studies have reported that being overweight or obese, but not morbidly obese, does not worsen prognosis. One large study including patients with Stage I-III breast cancer reported that underweight and morbidly obese women (≥40 kg/m(2)) had the highest risk of death compared to normal weight women (18.5 to < 25). Women classified as overweight (25 to < 30) did not experience an increased risk of death compared to normal weight women. Obese (30 to < 35 kg/m(2)) and severe obesity (35 to < 40 kg/m(2)) women had small increases in risk of death compared to normal weight women, but these increases were not statistically significant.
Being obese does not worsen Stage IV breast cancer prognosis
Although obesity can increase the risk of progression to stage IV breast cancer, it does not continue to worsen prognosis once the disease has reached this point. One major 2021 study reported that there was no significant link between being overweight or obese and survival in metastatic breast cancer patients. On the other hand, being underweight or having lost weight as of progression to stage IV disease is associated with poor outcomes, apparently because previous excess weight may have hidden ongoing cancer cachexia (loss of fat and muscle) which is typical of metastatic breast cancer patients starting long before death.
Below are links to 20 recent studies concerning this topic. For a more complete list of studies, please click on BMI.