Diet obesity and breast cancer an update

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Eur J Nutr. Cancer Epidemiol Biomarkers Prev. Int J Cancer ; 7 — Breast Cancer Res Treat , 1 — J Pharm Pharm Sci , 19 1 — Download references. The authors thank the members of the translational cancer research laboratory at the MD Anderson Cancer Center Foundation. You can also search for this author in PubMed Google Scholar. Correspondence to Laura Garcia-Estevez.

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Reprints and Permissions. Garcia-Estevez, L. Updating the role of obesity and cholesterol in breast cancer. Breast Cancer Res 21, 35 Download citation. Published : 01 March Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Background Breast cancer is the second most common cause of cancer-related death among women. Main text Obesity and cholesterol represent risk factors for breast cancer, but their impact is largely affected by cofounding variables including menopausal status, disease subtype, and inflammation.

Conclusions There is sufficient evidence that obesity and cholesterol impact clinical outcomes. Background Breast cancer is the most prevalent cancer in women and the second leading cause of cancer death worldwide.

Obesity and breast cancer prognosis Obesity and overweight have been linked with shorter all-cause and breast cancer survival. Table 1 Summary of studies investigating the association of obesity with breast cancer Full size table.

Full size image. Table 2 Summary of clinical studies investigating the association of cholesterol with breast cancer Full size table. Conclusion Overweight and obesity are intimately related with breast cancer development and recurrence. References 1. Article Google Scholar 3. Article Google Scholar 6. Article Google Scholar 7. Article Google Scholar 8. Article Google Scholar 9. While the false-negative rate was comparable among women with the entire range of BMIs, screen-detected cancers were identified more often and at a more advanced stage in obese women [ 8 ].

From this well-designed trial, it was concluded that neither patterns of use nor mammographic accuracy contributed to the increased incidence in obese women. Their findings were further reinforced by the publication of a more recent series. Psychosocial factors contribute to the challenge of diagnosing and treating obese women with breast cancer. In general, women of lower socioeconomic status are more likely to be obese than women of higher socioeconomic status and this may complicate access to medical care [ 10 ].

The stigma of obesity results in fear, fatalism, alienation, low self-esteem, and embarrassment, all of which contribute to lower adherence to screening and treatment guidelines [ 11 — 13 ]. Friedman et al. In-depth interviews of 33 women with a mean weight of pounds sd 45 were recorded for 60—90 min [ 14 ].

Those participants who followed through on cancer screenings shared certain personality traits compared with unscreened women, such as conscientiousness or self-regulatory ability, which allowed them to complete difficult or feared tasks. The attitudes of healthcare providers may also be a contributing factor in the creation of barriers to healthcare among obese patients.

All too frequently, healthcare providers may reflect negative societal attitudes toward obese individuals and this may impact perceptions, judgments, and decision making [ 15 ]. Patients who are obese are at increased risk for complications with anesthesia as they may be more difficult to intubate and maintain ventilatory support than normal-weight women.

An increase in the number of comorbid conditions associated with obesity further increases the risk of general anesthesia [ 16 , 17 ]. Breast-conserving surgery BCS or lumpectomy has the advantage of requiring less time in the operating room and therefore less time requiring anesthesia compared to mastectomy. Following BCS, patients receive radiation therapy to the breast and, depending on their stage, may receive regional nodal radiation as well. What is clearer is that the cosmetic outcome with breast conservation lumpectomy and radiation may not be as good in obese women compared to normal-weight women.

Serial assessments of breast cosmesis following lumpectomy and radiation therapy have identified persistent changes in the appearance of the breast. Two years after radiation, While small series from individual cancer centers have reported comparable rates of surgical complications in obese and normal-weight women undergoing mastectomy, larger series which include multiple institutions suggest otherwise. Recent data from the ACS-NSQIP database of women found that obesity was associated with an increase in both minor and major surgical complications, specifically increased risk of bleeding complications and surgical site infections [ 27 ].

Surgical staging of the axilla is determined by sentinel node mapping in which the primary lymph nodes involved in lymphatic drainage of the breast are removed in order to determine if breast cancer has spread beyond the breast.

This procedure has significantly reduced the number of women requiring axillary lymph node dissections, thereby decreasing the incidence of lymphedema [ 28 — 30 ]. However, data from large multi-institutional studies indicate that sentinel lymph node SLN identification rates are lower in obese women, and are associated with a higher failure to map rate [ 31 — 34 ]. With the rise in both rates of obesity and breast cancer, more obese women are seeking reconstruction following mastectomy.

Obese women may not be candidates for reconstruction due to limited reconstructive options or due to comorbidities. A recent systematic review of 29 studies demonstrated that obese women were significantly more likely to have surgical and medical complications following reconstruction compared to normal-weight women.

The rate of surgical complications was 2. Additionally, obese patients were 2. Complication rates are also higher in autologous-based flap reconstructions in obese patients and include flap failure both partial and complete , hematomas, necrosis, donor site infections, delayed healing of donor site, seromas, and hernias [ 36 — 39 ]. A separate systematic review evaluating the risk of complications in obese women undergoing breast reconstruction identified that a BMI of 40 was a threshold at which the rate of complications became prohibitively high [ 39 ].

Breast reconstruction is ultimately an elective procedure and the high risk of complications in this population may make surgery inadvisable. Additionally, obese patients undergoing breast reconstruction are more likely to be disappointed with the esthetic results [ 40 ]. Patients with large breasts may receive increased doses of radiotherapy to critical organs such as the heart or lungs owing to the positioning of the breasts on the chest wall when the patient lies supine [ 41 ].

Additionally, hypo-fractionated radiotherapy is possible in patients with large breast volumes; however, moist desquamation was found to be four times higher in patients with large breasts compared to those with smaller breasts [ 43 ]. Lymphedema LE is a dreaded complication of treatment for breast cancer. There are known risk factors associated with of the development of LE including the number of lymph nodes removed during surgery, development of surgical complications such as infection or seroma, use of chemotherapy, radiation therapy, and comorbid medical conditions, including obesity.

In a recent study, lymphedema rates were also found to be higher in patients undergoing axillary lymph node dissection, and among those with a more advanced stage of disease, in addition to having a higher BMI [ 12 , 14 , 32 ]. In the adjuvant setting, full doses of chemotherapy are associated with a greater improvement in overall survival [ 46 ]. The appropriate dosing of cytotoxic agents for obese women is challenging and underdosing may impact disease outcomes in obese women.

These guidelines were based upon a systematic review in adult survivors with breast, ovarian, colon, or lung cancer, and suggested that reduced doses of chemotherapy may result in poorer disease-free and overall survival. Importantly, there is no clear evidence that short- or long-term toxicities from chemotherapy are increased in obese breast cancer patients receiving full-weight—based doses.

The use of fixed-dose chemotherapy is only applicable for certain chemotherapeutic agents e. Ewertz et al. In this study, obesity was associated with an increased risk for developing distant metastatic disease and of dying of breast cancer. These findings were independent of tumor size, nodal status, and known prognostic factors, including HR status of the primary tumor [ 50 ].

The therapeutic dose of individual endocrine agents is fixed, regardless of weight or body surface area. In addition to the DBCCG study, other smaller series have reported less benefit from endocrine therapy in the obese population, independent of tumor size, nodal status, and known prognostic factors, including HR status [ 18 ].

These data collectively suggest a worse prognosis for overweight and obese women treated with endocrine agents and suggest that aromatase inhibitors may be less effective than tamoxifen in this population [ 52 ]. Fat is a metabolically active tissue with high levels of the aromatase enzyme which converts androgen to estrogen.

Excess estrogen production from expanded adipose tissue has been proposed as a possible mechanism for the adverse outcomes in obese women with breast cancer.

However, obesity is associated with adverse disease outcomes in obese women with hormone-sensitive and hormone-resistant cancers [ 18 ]. Furthermore, obesity is a risk factor for developing triple-negative breast cancer, which suggests that higher endogenous estrogens may not be the only mechanism contributing to a higher risk of recurrence [ 53 ].

Dysregulated inflammation in adipose tissues results in an accumulation of pro-inflammatory T cells and reduction in T regs, which contributes to obesity-related insulin resistance. STAT3 activity is increased in visceral adipose tissues and ablation of STAT3 in T cells has been shown to improve insulin sensitivity and glucose tolerance and reduce inflammation in visceral adipose tissues [ 54 ].

The biologic basis for the differences in the natural history of breast cancer in obese women is not completely clear. However, biologically active adipose tissues appear to be a contributing factor to the unique pathophysiology in obese women with breast cancer.

Obese women with breast cancer represent a unique patient population. They are at increased risk for the development of breast cancer and may experience more complications related to surgery and radiation. Despite appropriate local disease treatment, obese women are at increased risk for local recurrence compared to normal-weight women.

Similarly, systemic chemotherapy appears to be less effective, even when dosed appropriately on the basis of actual weight. In addition, endocrine therapy may be less effective in obese women, and there is a suggestion that tamoxifen may be more effective than the aromatase inhibitors in this population.

Taken together, these data suggest a unique and aggressive biology that is likely due to a tumor environment metabolically activated by adipose tissues. Overall, it is clear that the efficacy of cancer treatments is significantly lower in obese breast cancer survivors, posing greater challenges in patient care and disease management in this patient population. Based upon these challenges, further investigations are warranted to assess the effective diagnostic and treatment mechanisms needed to successfully target breast cancer within the obese patient population.

The authors thank Nicola M. Solomon, PhD, for editorial assistance and critical review of the manuscript. Drafting the article or revising it critically for important intellectual content: Kyuwan Lee, Joanne E.

Laura Kruper, Christina Dieli-Conwright. This article does not contain any studies with human or animal subjects performed by any of the authors. This article is part of the Topical Collection on Breast Cancer. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. National Center for Biotechnology Information , U.

Search database Search term. Abstract Obesity has a complicated relationship to both breast cancer risk and the clinical behavior of the established disease. Publication types Research Support, Non-U. Gov't Research Support, U. Gov't, P.