Tag Archives: breast cancer

The increase in bilateral mastectomy for treating breast cancer might not be justified

Cancer, Uncategorized, , , , , , , , , , , , , , ,
September 2014
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Bilateral mastectomy has become a common procedure to treat and to prevent breast cancer. The rate of bilateral mastectomy is increasing in the United States, in the United Kingdom, and also in Singapore among women with high grade and high risk of breast cancer1–3.

An observational study published this month on The Journal of American Medical Association4 compared the use and the mortality rate of bilateral mastectomy, unilateral mastectomy, and breast conserving surgery in 189,734 women diagnosed with stage 0–III breast cancer in California between 1998 and 2011. The team from the Cancer Prevention Institute of California and Stanford University found that bilateral mastectomy had an annual increase of 14.3% (from 2.0 % in 1998 to 12.3% in 2011), and it was more common among younger, white non-Hispanic women, with bigger and  higher grade tumors, higher education, and a private insurance. On the other hand, unilateral mastectomy was more diffuse in women older than 64 years, of Asian, Hispanic, and American Indian ethnicity, with large tumor size, high grade, and no private insurance. Compared with bilateral mastectomy, unilateral mastectomy was associated with 30% increased all-cause mortality; instead, there was no difference in mortality rate between bilateral mastectomy and breast-conserving surgery. Comparing all three procedures in early stage breast cancer patients, there was no benefit on survival associated with bilateral mastectomy over breast-conserving surgery; higher mortality was only associated with unilateral mastectomy.

This is the first study presenting a comparison among the three procedures. Other studies were published in the past comparing only two procedures at a time, but never all three together. The authors of this study state that maybe the use of bilateral mastectomy could be reduced, because there are no elements to support its benefits over other, less invasive treatments, such as breast-conserving surgery. This study was performed to identify whether the rise in bilateral mastectomies could be somehow justified, or whether the procedure could be substituted with a less expensive one. Bilateral mastectomy is an expensive procedure, and in a private healthcare system clinicians need to present supportive data to justify the selection of a procedure over another one.

If there are not enough data supporting this rise, the increase might have been caused by excessive precaution or fear. Whether it was fear or something else, patients have the right to know the real risks and benefits of each treatment based on actual data, because they are going to make the last decision, not the clinicians or the health policy makers.

 

  1. Trends in the use of bilateral mastectomy in England from 2002 to 2011: retrospective analysis of hospital episode statistics. Neuburger J, Macneill F, Jeevan R, van der Meulen JH, Cromwell DA. BMJ Open. 2013 Aug 1;3(8). pii: e003179. doi: 10.1136/bmjopen-2013-003179.
  2. Contralateral prophylactic mastectomy in an Asian population: a single institution review. Sim Y, Tan VK, Ho GH, Wong CY, Madhukumar P, Tan BK, Yong WS, Ng YY, Ong KW. Breast. 2014 Feb;23(1):56-62. doi: 10.1016/j.breast.2013.10.008. Epub 2013 Nov 23.
  3. Contralateral prophylactic mastectomy in women with breast cancer: trends, predictors, and areas for future research. Tracy MS, Rosenberg SM, Dominici L, Partridge AH. Breast Cancer Res Treat. 2013 Aug;140(3):447-52. doi: 10.1007/s10549-013-2643-6. Epub 2013 Jul 28. Review.
  4. Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011. Kurian AW, Lichtensztajn DY, Keegan TH, Nelson DO, Clarke CA, SL. JAMA. 2014 Sep 3, 312(9):902-14. doi: 10.1001/jama.2014.10707.

Light exposure at night induces resistance to therapy in breast cancer

Cancer, Uncategorized, , , , , , , , , , ,

The disruption of melatonin production during the night through light exposure reduces tumor latency and drives resistance to tamoxifen in a model of estrogen receptor positive alpha (ERa+) breast cancer.

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http://commons.wikimedia.org/wiki/File:Luz_en_Movimiento.jpg

Melatonin is an hormone mainly produced by the pineal gland in the brain and primarily regulates sleeping habits. Its production is light sensitive; therefore, it is produced only in complete darkness, and sleeping in synthetic lights can interfere with its production. Melatonin has also been involved in the regulation of reproduction, timing of ovulation, aging, immune function, and cancer1. In 2001 a study linked night shift rotation with a moderate increase in breast cancer risk2. Studies have shown that melatonin antagonizes the metabolism of linoleic acid, the most prevalent polyunsaturated fatty acid present in the Western diet that upregulates the expression of genes controlling ER expression, cell cycle, and growth.

A group led by Dr. Steven Hill at the Tulane University (Louisiana)3 investigated how disruption of melatonin production influences not only growth but also response to tamoxifen of ERa+ tumors implanted into rats (xenograft). They did two sets of experiments. In the first set they compared animals kept under normal conditions with animals kept under dim light exposure at night (dLEN); in the second set, they compared dLEN mice with dLEN mice supplemented with nighttime melatonin. They found that tumors implanted in the dLEN rats had a shorter latency and a 2.6-fold increase in the growth rate compared with the controls. These tumors were also totally resistant to tamoxifen, whereas the control animals responded to the therapy. The dLED tumors showed high levels of proliferative markers, increased metabolism, and low apoptosis. Strikingly, when the nighttime melatonin was supplemented in the dLEN mice, tumor growth latency was reduced and resistance to tamoxifen was reestablished, with reduction of metabolism, proliferation markers, and increase in apoptosis.

Many studies have shown that melatonin can affect tumor growth in different cancer models, but this is the first study involving melatonin in resistance to therapy. The resistance to tamoxifen is a big problem in the treatment of ER+ breast cancer; about 30% of patients show resistance, and the causes are not totally understood. Strikingly, this research indicates that melatonin disruption affects resistance to therapy, through a molecular mechanism that may involve ER phosphorylation. Several lifestyle habits can influence cancer risk, cancer development, and resistance to therapy—e.g. diet, smoking, exercise. In addition, this report indicates that even sleeping in the darkness might be more beneficial against cancer.

Sleep in the dark!

1Melatonin, sleep disturbance and cancer risk. Blask DE.Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17. Review.

2Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study.Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8.

3Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer. Dauchy RT, Xiang S, Mao L, Brimer S, Wren MA, Yuan L, Anbalagan M, Hauch A, Frasch T, Rowan BG, Blask DE, Hill SM. Cancer Res. 2014 Aug 1;74(15):4099-110. doi: 10.1158/0008-5472.CAN-13-3156.

Smoking Increases the Risk of Estrogen Receptor Positive Breast Cancer

Cancer, , , , , , , , , , , , ,

A study from the Fred Hutchinson Cancer Center shows that smoking among young women may increase the risk of developing estrogen receptor (ER)-positive breast cancer, but not triple negative breast cancer (TNBC).

The group led by Dr. Christopher Li conducted a population-based study among women from 22 to 44 years old diagnosed with breast cancer between January 2004 and June 2010 in the July 2014. The patients were 938 women in the control group, 778 in the ER-positive group, and 182 in the TNBC group. The researchers interviewed the patients and obtained detailed information about different aspects of their lifestyle—reproductive history, demographics, physical activity, alcohol drinking, medical history—and smoking habits—regency, number of cigarettes smoked per day, ages when smoked. The patients were divided in never smokers and ever smokers (current or former). The ever-smoker group was further categorized based on the number of pack of cigarettes smoked per year.

Smokers had increased risk of developing breast cancer overall (30%), without any significative change when the total number of years of smoking or the age women first started were considered. Although the small number of TNBC cases, the risk was associated with ER-positive breast cancer and not with TNBC. However, among current smokers, women who had been smoking for more than fifteen years had 50% increased risk of developing ER-positive breast cancer compared with women who had been smoking for fewer years. Of note is that, in women who had not been smoking for more than ten years the risk of developing ER-positive breast cancer decreased dramatically.

Various studies have correlated smoking to the risk of breast cancer, but this is one of the few studies linking smoking to ER-positive breast cancers in premenopausal women. Metabolites of tobacco, found in the breast fluid and breast tissue of current smokers, have been shown to have an estrogenic effect in in vitro studies, thus explaining the increased risk of ER-positive breast cancer in young women found in this research.

Smoking has several adverse effects and has been associated to different cancers. This is not only a study that supports previous reports linking smoking to breast cancer, but this study links smoking to a specific subtype of breast cancer (ER-positive) in young women.

 

Masaaki Kawai, Kathleen E. Malone, Mei-Tzu C. Tang, Christopher I. Li. Height, body mass index (BMI), BMI change, and the risk of estrogen receptor-positive, HER2-positive, and triple-negative breast cancer among women ages 20 to 44 years. Cancer, 2014

Legumes are better than meat for our health

Cancer, Nutrition, , , , , , , , , , , , ,

March2A study published this month on Cell Metabolism1 reveals that a diet high in meat proteins increases the risk for health-related diseases, whereas a diet rich in plant proteins  does not show the same adverse effects.

The team guided by Dr. Longo at the University of Southern California analyzed a nationally representative study sample of 6,381 subjects from the National Health and Nutrition Examination Survey (NHANES) III program with an average age of 65 years. Considering the entire group, a high and moderate protein diet was positively correlated with diabetes-related mortality, but not cancer mortality. When the population was divided into two groups –  50-65 years and  65 and older- , the protein intake showed different effects on subjects’ health. Subjects in the midlife group, consuming a high protein diet had a 74% increase in the risk of all-cause mortality and four-times increase in the risk of cancer mortality compared to the low protein group. In contrast, a high protein diet did not have the same negative effects on elderly subjects. Elderly subjects consuming a high protein diet had a reduction in both all-cause (23%) and cancer mortality (60%), when compared to a low protein diet.  This may be due to the fact that elderly people have impaired digestive and nutrient absorption abilities that can cause malnutrition and frailty; therefore a higher protein intake is beneficial at older ages to prevent diseases.

The authors link the effect of protein consumption on mortality to the insulin-like growth factor 1 (IGF-1) , showing that in humans an increase in IGF-1 is correlated with an increased risk of cancer in subjects 50-65 years old with a high protein diet. Instead, IGF-1 levels decrease in elderly subjects. They also performed experiments in mouse models demonstrating that a low protein diet is responsible for smaller melanoma and breast cancer cell derived tumors with circulating levels of IGF-1 correlating with the protein content in the diet. However, the mechanism of IGF-1 involvement  in protein intake and mortality is not well elucidated.

Despite the lack of a well-defined mechanism, this study demonstrates that a low protein diet in middle age people is beneficial for preventing cancer mortality through “at least, in part, regulating circulating IGF-1″. These findings are important in a country, the United States, where adults consume 1.0–1.3 g grams of proteins/kg of body weight/day, instead of the 0.7 to 0.8 g of proteins/kg of body weight/day recommended by the Food and Nutrition Board of the Institute of Medicine. According to previous reports, this study also shows that plant proteins, such as legumes, do not have the same unfavorable effect of animal proteins; in contrast, their intake has beneficial effects at all ages!

Beans might be healthier than hamburgers!

1. Morgan E. Levine, Jorge A. Suarez, Sebastian Brandhorst, Priya Balasubramanian, Chia-Wei Cheng, Federica Madia, Luigi Fontana, Mario G. Mirisola, Jaime Guevara-Aguirre, Junxiang Wan, Giuseppe Passarino, Brian K. Kennedy, Min Wei, Pinchas Cohen, Eileen M. Crimmins, Valter D. Longo. Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metabolism, 2014; 19 (3): 407-417 DOI: 10.1016/j.cmet.2014.02.006

Breast cancer survival: run, don’t walk,

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A recent Untitled-1 study from Dr. Paul T. Williams on International Journal of Cancer describes the benefits of intense physical exercises on breast cancer survival 1.

Physical activity improves our health conditions reducing the risk of many diseases, such as cardiovascular diseases, diabetes, and cancer. Previous studies linked regular physical exercises, even mild activity, with decreased breast cancer risk 2,3. Instead, the study reported here points out the importance of an intense physical activity over a mild activity.

Paul Williams from Lawrence Berkeley National Laboratory surveyed 986 breast cancer survivors, 272 runners and 714 walkers.  When the two groups where considered together, breast cancer mortality decreased proportionally to the hours of exercises (23.9% per metabolic equivalents-MET-hours/day). Instead, when the two groups were considered separately, breast cancer mortality was lower in runners than in walkers (66.5% difference), and in runners the mortality decreased proportionally to the hours of exercise (87.4% lower for 1.8 to 3.6 MET-hours/d). There was a correlation with age of death, suggesting that running was more effective in preventing mortality later than earlier in life. Although previous studies correlated BMI and adiposity with breast cancer mortality, in this report neither BMI, education, or diet influence the mortality. The incongruence might be due to the leaner cohort considered here, as pointed out by the same author. Physical activity alters metabolism, influencing blood concentration of different biomarkers used for breast cancer (estradiol, fasting insulin, and C-reactive protein), thus indicating a profound effect on its progression at the metabolic and molecular level.

As Williams discusses in the paper, this study presents some limitations, such as the small number of subjects. Moreover, although this study describes very accurately the information about women’s activity, it lacks some very useful information, such as data on the actual disease, receptor status, invasiveness, metastases or treatment. Given the low rate of mortality in this group, the women reported in this study seem to be a selected set of survivors with a less invasive disease.

Despite these limitations, the study presents for the first time the advantage of intense physical activity over mild activity, suggesting that exceeding the public health recommendations might be better for breast cancer survival, and probably for other health-related issues.

Therefore walking for 30 minutes for 5 days a week might not be enough!

 

  1. Paul T. Williams. Significantly greater reduction in breast cancer mortality from post-diagnosis running than walking. International Journal of Cancer, 2014; DOI: 10.1002/ijc.28740
  2. Hildebrand JS, Gapstur SM, Campbell PT, Gaudet MM, Patel AV. Recreational physical activity and leisure-time sitting in relation to postmenopausal breast cancer risk. Cancer Epidemiology, Biomarkers, and Prevention, October 2013
  3. Lauren E. McCullough, Sybil M. Eng, Patrick T. Bradshaw, Rebecca J. Cleveland, Susan L. Teitelbaum, Alfred I. Neugut, Marilie D. Gammon. Fat or fit: The joint effects of physical activity, weight gain, and body size on breast cancer risk.Cancer, 2012; DOI: 10.1002/cncr.27433

 

 

 

The first cancer drug for neoadjuvant treatment is on its way

Cancer, , , , , , , ,

October 2013At the beginning of September a group of experts, the FDA’s Oncologic Drugs Advisory Committee (ODAC), recommended accelerated approval of the Genentech’s drug Perjeta (Pertuzumab) for neoadjuvant treatment of early stage Her-2 positive breast cancers.

The Committee voted 13 to 0 with one abstention for the approval of Perjeta in combination with other two drugs, docetaxel and trastuzumab, another Genentech drug against Her-2. The FDA will return a verdict before the end of October. If approved, Perjeta is going to be the first nation’s cancer drug used to treat cancer patients before surgery with the purpose of shrinking the tumor to make it operable and allow breast conserving surgery.

Perjeta was approved by FDA in 2012 to treat metastatic HER-2 positive breast cancers after surgery. It is an antibody that binds to the Her-2 receptor inhibiting its activity by preventing the binding with other members of the Her-2 family.

The panel of experts based their decision on three clinical trials, two Phase II trials (NEUROSPHERE and TRYPHAENA) involving early breast cancer patients, and a Phase III trial (CLEOPATRA) with metastatic breast cancer patients. The NEUROSPHERE and TRYPHAENA were both conducted on patients with early stage Her-2 positive breast cancer, using two different regimen of chemotherapy.  NEUROSPHERE used Perjeta and Herceptin in combination with docetaxel, and TRYPHAENA used Perjeta and Herceptin in combination with anthracycline. The pathological complete response (pCR) was improved in both trials in patients using Perjeta in combination with the other drugs.  The increased efficacy of Perjeta combined with Herceptin is probably due to the binding of the two antibodies to two different regions of the Her-2 receptor, thus synergistically inhibiting its activation.

20% of breast cancer patients are Her-2 positive and those are the ones who are going to benefit from this treatment. This kind of tumor is very aggressive with 6,000 women dying every year in the US, mainly because of its inoperability. This drug will help to decrease the tumor volume, thus making it operable.

Genentech is part of the big Swiss pharmaceutical company Roche. Genentech has spent more than 30 years studying breast cancer leading to the commercialization of the first drug approved to treat Her-2 positive breast cancers, Herceptin. Genentech is going to lose the patent exclusivity for Herceptin in 2014 in Europe and 2018 in the US. Probably this market will be replaced by Perjeta…

This drug will treat breast cancer and Genentech’s budget.