Cancer News in Context: raloxifene

Showing posts with label raloxifene. Show all posts

Thursday, October 29, 2015

Practical Steps to Prevent Breast Cancer: Day 9 - If High Risk: Consider Risk-Reducing Medications

It's the final day in our nine day series highlighting key steps and practical tips that can help women lower their risk of breast cancer. Previous days.

_ _ _ _

If High Risk: Consider Risk-Reducing Medications

Although not commonly thought of as a “healthy behavior,” taking prescription risk-reducing medications – such as, tamoxifen, raloxifene, and possibly exemestane – can significantly lower the risk of breast cancer in women at high risk of the disease. They can also have important side effects, so they aren’t right for everyone.

“High risk” is specifically defined as a woman with a five-year risk of breast cancer of 1.67 percent or higher, typically calculated by the National Cancer Institute’s Breast Cancer Risk Assessment Tool. If you think you’re at high risk, either after estimating your risk or for some other reason, it’s important to talk to a doctor. Together, you can decide if risk-reducing medication or other steps to lower or manage your risk may be right for you.

Tips and Tricks – Tamoxifen and Raloxifine

Talk to a doctor about your risk and your options. Many women who feel they’re at high risk are likely not. And some who feel they aren’t, likely are. So it’s important to talk to a doctor or other qualified health professional about your risk of breast cancer. If you are at high risk, together you can talk about your options for managing that risk and decide which option is likely best for you.

Review the possible benefits and risks of risk-reducing medication. For many high-risk women, tamoxifen, raloxifene, and possibly exemestane are good choices for managing their risk. Though each does have potential side effects, these can be dramatically offset by their ability to cut the risk of breast cancer in half. Talk to a doctor about how these might balance out for you. A huge percentage of women in the United States who stand to benefit greatly from risk-reducing medications choose not to take them – and not always for accurate reasons (more).

Next Steps – Tamoxifen and Raloxifene

American Cancer Society
http://goo.gl/dyHRbS

National Cancer Institute
http://www.cancer.gov/bcrisktool

Your Disease Risk
http://yourdiseaserisk.wustl.edu

Excerpted from TOGETHER - Every Woman's Guide to Preventing Breast Cancer

Photo: Walking on the beach by Hernan Pinera (CC License, CC BY-SA 2.0)(adapt: black & white)

Tuesday, July 29, 2014

Missed Opportunities to Prevent Cervical Cancer: Use of HPV Vaccine Still Low

Photo: Flickr/Melissa Wiese

To work in the field of cancer prevention one has to be an optimist at heart. In the science, in the statistics, and in the news, you see not only the broad burden of cancer but also the vast opportunities that exist to lower risk and prevent the disease.

At the same time, we understand that shifting environments, attitudes, and behaviors in positive directions can take years, and most likely decades. We didn't overnight become a nation where two-thirds of us are overweight/obese and half of us get little or no activity. So it follows that shifting the pendulum in the other direction won't happen overnight either. Such issues take daily efforts year after year to address both on a personal level and on a societal level. There are no magic bullets.

Yet, however optimistic, there are two issues that leave many in the public health and medical professions scratching their heads over: the underuse of two relatively simple medical strategies that have vast potential for preventing cancer.

We've written at length about both of these strategies here in CNiC: the use of medications to prevent breast cancer in those at high risk of the disease (posts), and the use of the HPV vaccine to prevent cervical cancer (posts).

Of these two, the low use of the medications tamoxifen and raloxifene is perhaps the hardest to understand, given the large demonstrated benefits they have in preventing breast cancer in high risk women and the yawning gap between the number of women who likely stand to benefit from taking them (well over 2 million) and the number who actually do take them (just 117,000).

While new data on the HPV vaccine show there's been some progress in its use, the numbers also fall well short of what should be possible based on the use of other standard childhood vaccines. The vaccine is recommended for all girls and boys ages 11 or 12, given in a three dose course. Its safety has been well-documented. Yet, only 57% of girls and 35% of boys get one or more doses of the vaccine. Count only those who've received the full three doses, and the numbers fall to 38% for girls and 14% for boys. Based on the number of children in this age-group cohort who receive other vaccines at their standard health care visits, and these percentages could realistically be as high as 91%.

The primary reasons parents give for not vaccinating their children were similar for both girls and boys, including the vaccine not being recommended by the health care provider, concerns about safety, and lack of knowledge of the vaccine or feeling it wasn't needed.

Both of these cases - low use of the HPV vaccine and of tamoxifen/raloxifene - demonstrate just how important broad-based efforts at education are. It is not enough to demonstrate cancer prevention benefits - even benefits from activities as relatively simple as getting a vaccine or taking a pill. Concerns of patients, parents, and health care providers must be appropriately addressed while we also move ahead fostering knowledge of, and demand for, the benefits the vaccine and preventive medications provide.

The trend in HPV vaccination show's we're making some progress on that front. We have to be happy with that, but as usually, we'll keep striving for more.

Tuesday, June 25, 2013

More evidence of powerful breast cancer prevention

We have previously pointed to the strong evidence that use of selective estrogen receptor modulators (SERMs) substantially reduces risk of breast cancer. New updated data has been published in the British journal Lancet (May 25, 2013). The original data from all patients in a number of trials of these agents for prevention for breast cancer were combined using common analytic methods. The authors report that across 9 prevention trials and 83,339 women randomized to SERMS and followed for an average of 65 months, had a significant 36% reduction in invasive breast cancer. The reduction in risk is stronger for estrogen receptor positive breast cancer.

New insights in this report include the protection from taking SERMs persists for 5 or more years after stopping. Also risk of vertebral (spine) fractures was significantly reduced by 34%. This improves the benefit to risk trade-off that this and other drug based prevention strategies require.

The good news is that the adverse effects form taking SERMs are now well documented and low frequency.

From this analysis the authors draw on the extended follow-up and estimate that for every 42 women treated with a SERM for 5 years one case of breast cancer will be prevented within 10 years of beginning therapy. This is similar to our early post in which we pointed to our paper from 2008 showing that for 5 years of use among women 65 to 69 one case of invasive breast cancer would be prevented for every 43 women treated, and for women 60 to 64 in the top 10% of breast cancer risk in the population, one case would be prevented for every 53 women given the chemoprevention drug.

We recently noted that use of SERMs is much lower than might be expected given the substantial reduction in breast cancer with use of these drugs. The FDA approved the use of Tamoxifen for primary prevention of breast cancer in both premenopausal and postmenopausal women at high risk. This approval was in 1998. In 2007, the FDA approved Raloxifene for primary prevention of breast cancer among postmenopausal women.

See earlier posts: Cancer News in Context: Breast Cancer Prevention

And for breast cancer prevention, see: Cancer News in Context: Breast cancer prevention

Wednesday, April 24, 2013

Risk-Reducing Medications for Women at High-Risk of Breast Cancer: New Recommendations and Missed Opportunities

The United States Preventive Services Task Force (USPSTF) recently came out with a new draft statement on the use of medications that can reduce the risk of breast cancer in women at high-risk of the disease (draft statement). The statement recommends that women at high risk of breast cancer - and low risk for medication side effects - be offered prescription risk-reducing medications, like tamoxifen or raloxifene. The decision on whether or not to take the medication should be made as a shared decision between a patient and her physician.

Tamoxifen and raloxifene are approved by the FDA for use in preventing breast cancer in women at high risk of the disease, which is typically defined as a 1.67 percent chance or greater of developing breast cancer over a five year period. Tamoxifen is approved for women age 35 and older, while raloxifene is approved for post-menopausal women. Since the risk of the disease goes up with age, a 1.67 percent risk essentially translates to the 5-year risk of an average woman 60 years old or over. (To see where your risk falls, visit the National Cancer Institute Breast Cancer Risk Assessment Tool.) This means approximately 10 million women in the United States are eligible for using these medications for prevention.

Yet, their current use is astonishingly low, especially given that breast cancer is a disease so feared by many women and that the medications have been demonstrated in clinical trials of high-risk women to cut the long term risk of breast cancer by 50 percent.

A recent study by Erika Waters and colleagues found that only about 117,000 women (well under one percent) in eligible age groups were taking either tamoxifen or raloxifene - a number that has basically remained steady since the year 2000.

So what keeps more women from taking these risk-reducing medications? Evidence shows that it's the potential risk of side effects that likely sways eligible patients away from using - and their doctors from prescribing - tamoxifen or raloxifene. Side effects, of course, are an important consideration when deciding whether or not to take any medication, and potential harms of tamoxifen and raloxifene, while rare, can be serious - including, stroke, blood clots, and uterine cancer. So, it's good that many women approach them with caution.

Yet, simply knowing the side effects of these drugs isn't enough to provide a full picture of their ability to help or harm women. It's important to know the likelihood that a woman might experience side effects and to put this into context with the potential breast health benefits. It is here where it can be hard for patients - and even their doctors - to properly balance the harms and benefits of these drugs and decide when the benefits are likely to outweigh the harms.

It certainly makes sense that no woman wants to trade one serious risk for another - lowering, say, breast cancer risk but upping stroke or endometrial cancer risk an equal amount. But, reviews of evidence show that there are some pretty clear groups of women for whom the benefits of tamoxifen or raloxifene outweigh the potential harms.

The draft Task Force recommendation states that, overall, the benefits of risk-reducing medications start to outweigh the harms when the 5-year risk of breast cancer hits 3 percent or greater. Based on the same evidence, National Cancer Institute researchers have described in detail in women age 50 and older which groups of women are likely to benefit from risk-reducing medication based on age, race, risk level, and whether or not a woman has had her uterus removed. In general, the younger a woman is and the higher her risk, the more likely the benefit from taking risk-reducing medications will outweigh the potential harms.

The tables below show the 5-year risk for different groups where the risk-lowering benefits of tamoxifen or raloxifene are likely to outweigh the harms. Because tamoxifen can raise the risk of uterine cancer - and raloxifene does not - raloxifene is recommended over tamoxifen in women over 50 who still have a uterus. For women without a uterus, the potential harms and benefits of tamoxifen and raloxifene are similar.

That so many women at increased risk of breast cancer choose not to take tamoxifen and raloxifene is a health paradox. "In many stories of medical advancements, it's the risks that frequently get hidden in the news headlines, but with tamoxifen and raloxifene, it seems it's just the opposite," says Graham Colditz, MD, DrPH, a Professor of Surgery at Washington University School of Medicine and Associate Director of Prevention and Control at the Siteman Cancer Center. "The harms seem to get over-played in relation to the benefits. This leaves many women and their doctors passing up what science shows is a great chance to halve their risk of breast cancer. It's a huge opportunity missed."

References

Freedman AN, Graubard BI, Rao SR, McCaskill-Stevens W, Ballard-Barbash R, Gail MH. Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention. J Natl Cancer Inst. 2003;95(7):526-32.

Freedman AN, Yu B, Gail MH, Costantino JP, Graubard BI, Vogel VG, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29(17):2327-33. PMCID: 3107748.

Waters EA, McNeel TS, Stevens WM, Freedman AN. Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010. Breast Cancer Res Treat. 2012;134(2):875-80.

Tuesday, January 3, 2012

Medical interventions to prevent cancer

Much has been written over the past few months on progress against cancer. For example, in the New York Times, Kolata summarizes funding for cancer research and shows the percentage of health research funding spent on cancer treatment research, cancer biology, and cancer causation, with only a small fraction on early detection and prevention (1). This reflects the commitment made forty years ago, when the U.S. declared war on cancer, and promised a cure. While treatment and biology gain the predominant funding, we should remember that there are proven ways to prevent cancer, some through lifestyle changes, and others through medical interventions. While medical interventions may most often be focused on high-risk men and women, we know that smoking cessation – a population wide strategy – can reduce both incidence of many cancers and mortality from cancer.

Smoking cessation powerfully reduces lung cancer and total mortality as demonstrated in Figure 1. Compared to continuing smokers, those who successfully quit have a 20% reduction in lung cancer mortality within 1 to 4 years of quitting and a 40% reduction within 5 to 9 years (2). Smoking cessation also reduces total mortality by 13% in less than 5 years and by 33% in less than 10 years, due to the additional benefits of reduced risk of cardiovascular death and other smoking-related cancer deaths (2). Thus, the benefits for smoking cessation are unarguable.

On the other hand, seeking technologic solutions, the randomized clinical trial for screening smokers with CT scans, showed a 20% reduction in lung cancer mortality after an average of 6 years of follow-up, and a reduction in total mortality of 6.7% (9).

But there are other research-proven strategies and interventions to prevent much of cancer outright.

We might consider these as drugs (aspirin, selective estrogen receptor modulators), vaccines, and screening or surgical interventions. While the time frame from intervention to benefit varies for the cancers, most of these medical interventions result in substantial benefits and typically the benefits outweigh the risks of exposing the population to the medical procedures. For example, we estimated that a large proportion of postmenopausal women would benefit from Raloxifene (a SERM) and given its relative positive trade off of benefits to risk, its widespread use could result in a substantial reduction in postmenopausal breast cancer (3). Likewise, for aspirin which is recommended for men over 45 to reduce risk of cardiovascular disease, and for women over 55 to reduce risk of cerebrovascular disease (4), the benefits for colon and other cancer risk reduction over 20 or more years of use are substantial (5). Perhaps the reduction in cancer is an unintended benefit of widespread use to reduce cardiovascular disease risk.

Vaccines, on the other hand, more typically considered a population-wide interventions, take decades to observe the benefit of reduced cancer incidence, and require broad implementation to achieve reduction in the cancer burden for the whole population. Several countries have embarked on more traditional public health strategies for HPV vaccine (Australia, mandatory) and hepatitis vaccine programs (e.g., Taiwan) to achieve reductions in the burden of cancer.

In the table below, we summarize the target for each intervention, the magnitude of reduction in cancer that has been observed following interventions, and the source of evidence for each intervention.

Table. Proven cancer prevention interventions using medical interventions

Intervention	Target	Magnitude of reduction	Evidence
Aspirin	Total cancer mortality	20% reduction	Follow-up of 8 RCT (5)
Aspirin	Colon cancer	40%	Five RCTs (6) and RCT in Lynch syndrome (7)
SERMs Tamoxifen Raloxifene	Breast cancer incidence	40 to 50%	RCT (8, 9)
Salpingo oophorectomy	Familial risk of breast cancer	50%	Observational data synthesis (10)
Screening for colon cancer Sigmoidoscopy (RCT) Colonoscopy	Colon cancer mortality	Sigmoiodoscopy 30% to 40% in 10 years Colonoscopy – 50%	UK RCT sigmoidoscopy (11) observational data
Vaccines HPV Hepatitis, etc	Cervical cancer Liver cancer		(12, 13)
Mammography	Breast mortality	30%	RCT refs
Spiral CT for lung cancer	Lung ca mortality	20% in 6.5 yrs	RCT (14)