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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).

In the US, breast cancer is the most common female cancer,
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
one third of US adults are obese.

.

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

.
Obesity and Breast cancer
(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.
.‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬
Sestak 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
in obese women after menopause due to increased adipose
tissue mass and up-regulation of aromatase.Thus, estrogensensitive tissues are exposed to more estrogen stimulation
which can stimulate the growth and progression of breast
cancer.
Altered production of adipokines by adipocytes: Plasma leptin
concentrations (which promotes breast tumor growth) are
elevated in obese women, whereas adiponectin levels (which
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
Obesity and Breast cancer
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
(BMI) under 25kg/m2 Through out their body Mass index
adult lives.
‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬
Petrelli JM, Calle EE, Rodriguez C, et al: Body mass index, height, and Postmenopausal breast cancer
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.

‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬
JenK L, Djuric Z, DiLaura NM, et al: Improvement of metabolism among obese breast cancer
survivors in differing weight loss regimens. Obes Res
2004 ,312-306 :12
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.
‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬
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 and Breast cancer
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.
Obesity and Breast cancer

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Obesity and Breast cancer

  • 1. Obesity and Breast Cancer by Osama Elzaafarany Ass. Lecturer of clinical oncology Department of Cancer Management and Research Medical Research Institute Alex. University
  • 2. 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). In the US, breast cancer is the most common female cancer, the second most common cause of cancer death in women, and the main cause of death in women ages 40 to 59.
  • 3. 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
  • 4. 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.
  • 5. 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 one third of US adults are obese. . Flegal KM, Carroll MD, Ogden CL, et al: Prevalence and trends in obesity Among US adults, 1999-2008. JAMA 303: 235-241, 2010
  • 6. Impact of obesity on breast cancer prognosis & treatment
  • 7. (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
  • 8. 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. ‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ Ewertz M, Jensen M-B, Gunnarsdo´ttir KA, et al: Effect of obesity on Prognosis after earlystage breast cancer. J Clin Oncol 29: 25-31, 2011 .
  • 10. (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. .‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ Sestak 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
  • 11. Why obesity increases the risk of breast cancer and leads to poor prognosis ?
  • 12. Increased production of estrogen In excess adipose tissue in obese women after menopause due to increased adipose tissue mass and up-regulation of aromatase.Thus, estrogensensitive tissues are exposed to more estrogen stimulation which can stimulate the growth and progression of breast cancer. Altered production of adipokines by adipocytes: Plasma leptin concentrations (which promotes breast tumor growth) are elevated in obese women, whereas adiponectin levels (which has direct anticancer effects, many of which are mediated through adenosine monophosphate–activated protein kinase) are reduced.
  • 13. 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.
  • 14. 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
  • 15. 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
  • 17. 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 (BMI) under 25kg/m2 Through out their body Mass index adult lives. ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ Petrelli JM, Calle EE, Rodriguez C, et al: Body mass index, height, and Postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Causes Control 13: 325-332, 2002
  • 18. 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. ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ JenK L, Djuric Z, DiLaura NM, et al: Improvement of metabolism among obese breast cancer survivors in differing weight loss regimens. Obes Res 2004 ,312-306 :12
  • 19. 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
  • 20. 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. ‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ 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
  • 21. 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.
  • 23. 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.