Weight loss decreases breast cancer risk in postmenopausal women

October is breast cancer awareness month, which an annual campaign to increase the awareness about the deadly disease. With over 2 million new cases every year, it is the most prevalent cancer in women. Although breast cancer runs in families, there are other lifestyle and environmental factors which increase the risk of breast cancer.

Obesity increases the risk of postmenopausal breast cancer; the risk is 1.5 times higher in overweight women and about 2 times in obese women than healthy weight women. The association between weight loss and incidence of breast cancer is inconsistent, and few studies have evaluated the association between the two.

 A recent observational study by Chlebowski RT et al. published in Cancer, the peer-reviewed journal of the American Cancer Society reported that women decreased the risk of breast cancer by 12% if they lost weight in 3 years as compared to the ones whose weight remained stable.

“Obesity is associated with increased risk of incident postmenopausal breast cancer,” Rowan T. Chlebowski, MD, Ph.D., research professor in the department of medical oncology and therapeutics research at City of Hope National Medical Center, and colleagues wrote. “Because approximately one-third of postmenopausal women in the United States are obese, obesity represents a common and potentially modifiable factor related to breast cancer outcome. However, it has not been established that weight loss in postmenopausal women decreases breast cancer incidence or breast cancer mortality.”

The researchers from the Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California used data from the Women’s Health Initiative (WHI) Observational Study to study the association.

The study included 61,335 postmenopausal women with no prior history of breast cancer and normal mammogram with body weight and height measured and body mass index (BMI) calculated at baseline and after 3 years.

At the end of 3 years, the analysis was based on 3 weight categories: stable, 5% increase or 5% decrease.

The study participants were between 50 to 79 years, and the mean follow-up duration was 11.4 years, during which the researchers observed 3,061 cases of breast cancer.

Women (n = 8175) who lost weight faced a 12% decreased risk of breast cancer as compared to women whose weight remained stable (n = 41,139) (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.78‐0.98; P = .02). The association remained the same even after adjustment for mammography.

The mean time to develop breast cancer was 6.5 years after the 3-year weight determination.

Women who gained (≥5%) weight (n = 12,021) were not associated with increased risk of breast cancer (HR, 1.02; 95% CI, 0.93‐1.11) but did show a slightly higher incidence of triple‐negative breast cancer (HR, 1.54; 95% CI, 1.16‐2.05).

“Our study indicates that moderate, relatively short-term weight reduction was associated with a statistically significant reduction in breast cancer risk for postmenopausal women,” said Dr. Chlebowski in Wiley press release. “These are observational results, but they are also supported by randomized clinical trial evidence from the Women's Health Initiative Dietary Modification trial where, in a randomized clinical trial setting, adopting a low-fat dietary pattern that was associated with a similar magnitude of weight loss resulted in a significant improvement in breast cancer overall survival. These findings, taken together, provide strong correlative evidence that a modest weight loss program can impact breast cancer.”

Here is the visual abstract of the study.

Abstract

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FDA broadens the age range of Gardasil 9 to cover individuals 27 through 45 years old

The US Food and Drugs Administration (FDA) extended the use of Merck’s cervical cancer vaccine Gardasil 9 to include men and women aged 27 through 45 years.

"Today's approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range," Peter Marks, MD, Ph.D., director of the FDA's Center for Biologics Evaluation and Research, says in a news release.

"The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90% of these cancers, or 31,200 cases every year, from ever developing," Marks says.

 "The CDC has made increasing HPV vaccination rates a public health priority,” said Jacques Cholat, M.D., president, Merck Vaccines, “and today’s recommendation for GARDASIL 9 is an important milestone in the shared effort to help further reduce the burden of HPV-related cancers and diseases.”

According to CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with, and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women. 

FDA first approved Gardasil in 2006, to prevent certain cancers and diseases caused by HPV Types 6, 11, 16, and 18. Gardasil is no longer available in the US. Gardasil 9 received approval in 2014 for use in girls and women 9 through 26 years of age and boys 9 through 15 years of age for the prevention of the cancers and precancerous lesions of cervix, vulva, vagina, and anus caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

The approval is based on results of a study involving 3,200 women, aged 27 through 45 years, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine.

"The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long-term follow-up from this study," the FDA said.

Similarly, in men aged 27 through 45 years of age, vaccine effectiveness was inferred based on data described above in women, along with efficacy data of Gardasil 9 in younger men aged 16 through 25 years, and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

In all the safety and efficacy of Gardasil 9 was evaluated in a total of 13,000 males and females, the most commonly reported side effect being injection site pain, swelling, redness, and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

Important Information about GARDASIL 9 (Human Papillomavirus 9-Valent Vaccine, Recombinant)

GARDASIL 9 does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening.

Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care provider.

GARDASIL 9 has not been demonstrated to protect against disease from vaccine HPV types to which a person has previously been exposed through sexual activity.

GARDASIL 9 has not been demonstrated to protect against diseases due to HPV types other than 6, 11, 16, 18, 31, 33, 45, 52, and 58.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52 and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

FDA press release

Merck news release

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News from ASRM 2018: Some interesting research papers on male factor infertility

The American Society of Reproductive Medicine just wrapped up its 2018 scientific congress and expo at Denver, Colorado.  Here are some of the research highlights presented at the society about male factor infertility. 

A diagnosis of azoospermia puts men at increased risk of death

Results of a large prospective cohort study report a link between azoospermia and increase the risk of mortality. The study findings were jointly presented by Scandinavian and American researchers at the meeting. Interestingly, the increased risk of dying was not observed for men with oligospermia. 

The authors analyzed data of 51,289 men from the Danish National IVF register from 2006 through 2016 and followed those with azoospermia till the end of study period, death or till they emigrated from Denmark. Vasectomized men and men with normal semen parameters were used as a reference.

The average follow-up period was eight years. Men with azoospermia faced twice the increased risk of dying as compared to men with oligospermia and normal semen parameters.  The mean age at death was 48.8, and the most common cause of death was CVD and cancer.  

Another previous cohort study from Denmark also documented that as the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05).

Peter Schlegel, MD, ASRM President-Elect, noted, “A man’s infertility status is a component of his whole health status. Semen analysis results exist on a continuum, but a diagnosis of azoospermia may be a call to take a closer look at a man’s overall health in addition to his reproductive function.”

Thus, Semen parameters could be a key biomarker of overall male health.

Abstract: Male factor infertility and risk of mortality: a register-based cohort study

Inadequate sleep is linked to Low Testosterone Levels in Men

Lack of sleep is associated with decreasing testosterone levels in US male reports the results of a study presented at the ASRM scientific congress at Denver, Colorado. The other culprits for low testosterone were aging, increasing BMI and alcohol consumption.

The researchers examined the data on nearly 2300 males, aged 16-80 years from The National Health and Nutrition Examination Survey (NHANES). The subjects reported an average sleep duration of 6.86 hours (2-12 hours) and had average serum testosterone levels of 303.33 ng/dL (43.39 ng/dL to 779.2 ng/dL).

After accounting for confounders, the researchers noted that serum testosterone levels decreased by 0.49 ng/dL per year of age, 5.85 ng/dL per lost hour of sleep, 6.18 ng/dL per BMI unit increase, and 2.99 ng/dL per each unit increase in alcohol consumption.

Robert Brannigan, MD, a member of ASRM’s Board of Directors, remarked “Reduction in testosterone level can have deleterious effects on a man’s health beyond his fertility and sexual function.  Testosterone is essential for good metabolic function and decreased levels of the hormone are associated with metabolic syndrome and cardiovascular disease.  Low testosterone can contribute to fatigue and depression, as well. A balanced diet and a healthy sleep routine are interventions a man can take on his own to help keep his T levels stable.”

Abstract: Impaired sleep is associated with low testosterone in us adult males: results from the national health and nutrition survey

A decline in sperm count and motility observed in North America and Europe

Two studies presented at the ASRM scientific congress showed that semen quality has seen a decline in patients undergoing fertility treatment and donors in this century. In the first study, researchers from one European and the other North American center evaluated the results of semen analysis from 119,972 men seeking infertility treatment between 2002 through 2017.

The researchers looked at the most reliable indicator of male fertility, the total motile sperm count (TMSC) and grouped the study population into 3 groups: TMSC greater than 15 million; TMSC 5 to 15 million: and TMSC zero to 15 million.

The percentage of patients in Group 1 (highest TMSC) declined from 84.7% in the time period 2002-2005 to 79.1% in 2014-2017, while the percentage in Group 3 (lowest TMSC) rose from 8.9% to 11.6% over those time periods.

TMSC decreased by 1.1% per year as the men aged and thus patients who belonged to Group 1 were slowly slipped into Group 2 as they age.   

For the second study researchers from the Ichan School of Medicine at Mount Sinai, California Cryobank, and Reproductive Medical Associates of New York observed a progressive decline in semen quality in donors over 11 years in six cities:  Los Angeles, Palo Alto, Houston, Boston, Indianapolis, and New York City.

Over a period of 10 years, the researchers analyzed 124,107 semen specimens provided by 2586 donors aged 19 to 38. They looked at three semen parameters- total count, average concentration, and TMSC-  as a whole and region by region.

A decrease in all three parameters was observed in all regions, except New York. ASRM President-elect Peter Schlegel, MD, said, “The trend toward lower sperm counts in this study is concerning.  Whether the causes underlying it are environmental or lifestyle-related, they will be difficult to parse out.  Pollution, endocrine disrupting chemicals, poor exercise habits and convenient, yet nutritionally poor, dietary choices could all play a part.  Similarly, men may now be referred for advanced medical care despite having lower sperm numbers, reflecting our improved reproductive treatments.  Men planning to conceive should do what they can to achieve their best overall health to optimize their sperm quality.”

Abstract: Total motile sperm count trend over time across two continents: evaluation of semen analyses from 119,972 infertile men

Abstract: Eleven-year longitudinal study of U.S. sperm donors demonstrates declining sperm count and motility

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