Obesity

and

Breast Cancer

by

Osama Elzaafarany Ass. Lecturer of clinical oncology

Department of Cancer Management and Research Medical Research Institute

Alex. University

Incidence of breast cancer

Breast cancer is the most common malignancy in

Women in the UK. At the year 2008 it was reported that more than 40000 women in the UK develop breast cancer each year (which accounts for 29% of all cancer in women).

,most common female cancerIn the US, breast cancer is the

the second most common cause of cancer death in women,

and the main cause of death in women ages 40 to 59.

The American Cancer Society estimated that 229.060 new cases of breast cancer will be diagnosed in US at 2011.

The incidence of breast cancer

has increased steadily in US over

the past few decades but breast

cancer mortality appears to be

declining, suggesting a benefit

from early detection and more

effective treatment

Breast cancer in Egypt: According to official statistics of the National Cancer Institute (Cairo University), breast cancer accounts for 35.7% of the cases of cancer in Egypt and is the most prevalent cancer among Egyptian women. In Egypt, the median age at diagnosis for breast cancer is ten years younger than in the United States and Europe.

Incidence of obesity:

The percentage of over weight and obese adults and children has been steadily increasing during the last two decades, and it is estimated that

of US adults are obese. one third

.

Flegal KM, Carroll MD, Ogden CL, et al: Prevalence and trends in obesity

Among US adults, 1999-2008. JAMA 303: 235-241, 2010

Impact of obesity on breast cancer prognosis &

treatment

(I) Impact on prognosis:

weight gain, and obesity account for approximately 20% of all cancer cases.

Obesity is an

established

risk factor for the

development of

postmenopausal

breast cancer

A retrospective study by Ewertz et al, published at 2011

reported that obesity is an independent prognostic factor for the development of distant metastases and death after the diagnosis of breast cancer.

Also obesity is associated with an increased risk of recurrence in women who have breast cancer.

And Adjuvant treatment seems to be less effective in obese women.

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.Ewertz M, Jensen M-B, Gunnarsdo´ttir KA, et al: Effect of obesity on Prognosis after early-stage breast cancer. J Clin Oncol 29: 25-31, 2011

(II) Impact on treatment:

1) Obese patients will experience excessive toxicity

when drugs are dosed on the basis of actual body

weight.

2) Obesity may also reduce the efficacy of endocrine treatment in patients with breast cancer; in a study published at 2010, the use of the aromatase inhibitor (anastrozole) was associated with a significantly greater risk of breast cancer recurrence in overweight versus lean women who were postmenopausal as the standard dose of anastrozole may have been insufficient to fully suppress the high estrogen

Levels found in obese women.

. ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــSestak I, Distler W, Forbes JF, et al: Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: Anexploratory analysis from the ATAC trial. J Clin Oncol 28: 3411-3415, 2010

Why obesity increases the risk of breast cancer and leads to poor

prognosis ?

Increased production of estrogen In excess adipose tissue

increased adiposein obese women after menopause due to

-.Thus, estrogenregulation of aromatase-upand tissue masssensitive tissues are exposed to more estrogen stimulation which can stimulate the growth and progression of breast cancer.

leptinby adipocytes: Plasma adipokines Altered production of concentrations (which promotes breast tumor growth) are

levels (which adiponectinelevated in obese women, whereas has direct anticancer effects, many of which are mediated through adenosine monophosphate–activated protein kinase) are reduced.

Obesity-related effects on insulin Levels which has mitogenic, antiapoptotic, and proangiogenic properties, and the release of insulin-like growth factor-1(IGF-1) which has multiple effects that have been linked to tumor growth and metastasis.

Obesity is recognized as a Pro-inflammatory state as it results in the release of inflammatory Mediators from activated macrophages in adipose tissue including tumor necrosis factor α, interleukin-1β and interleukin-6 (IL-6) that promote tumor growth.

�

Pathways that directly link obesity with breast cancer.

Sinicrope F A , Dannenberg A J JCO 2011;29:4-7

©2011 by American Society of Clinical Oncology

Figure 1 Molecular mechanisms supporting a causal link between obesity and breast cancer.

Lorincz A M , Sukumar S Endocr Relat Cancer 2006;13:279-292

© 2011 Society for Endocrinology

It has been estimated that 11,000 to 18,000

deaths per year as a result of breast cancer in US women age 50 years or older might be avoided if women maintained a

body Mass index (BMI) under 25kg/m2 Through out their adult lives.

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mortality in a prospective cohort of US women. Cancer Causes Control 13: 325-332, 2002

Both the endocrine and metabolic changes that are associated

with obesity are reversible by body weight reduction.

Specifically, losing at least 10% of body weight was shown to reduce the Concentrations of estradiol, leptin, and insulin in sera.

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JenK L, Djuric Z, DiLaura NM, et al: Improvement of metabolism among obese breast cancer

survivors in differing weight loss regimens. Obes Res

12: 306-312, 2004

So changes in diet and increased physical activity to achieve a healthier body weight are a cancer-prevention strategy that may also improve the prognosis of patients with curatively resected breast and other cancers

New pharmacologic approaches that target pathways that are deregulated in obesity may also prove beneficial.

Metformin; an anti-diabetic drug showed a Significant reductions in plasma insulin and body weight when evaluated in non-diabetic early breast cancer patients, which suggests the potential benefits of metformin for breast cancer prevention or treatment in obese women.

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Goodwin PJ, Pritchard KI, Ennis M, et al: Insulin-lowering effects of Metformin in women with early

breast cancer. Clin Breast Cancer 8: 501-505, 2008

Future directions

Newer drugs that target obesity-related pathways are being developed, including agents targeting the IGF-1 and adiponectin receptors.

Additional study is needed to determine whether these agents will prove useful in the management of breast cancer in obese women.

Obesity is a risk factor for breast cancer in a postmenpausal women.

Obesity associated with poor prognosis in breast cancer by various mechanisms.

Management of obesity can improve outcome in breast cancer.