Watching Women's Health

Self and clinical breast exams not as helpful we thought

My last two posts addressed mammogram recommendations in the recent US Preventive Services Task Force (USPSTF) report on breast cancer screening. I also have some thoughts about the task force's comments on self and clinical breast exams.

For decades, physicians and breast cancer advocacy groups have recommended a monthly self breast exam (SBE) for adult women. I am not sure exactly when or from where this concept originated.

Monthly SBE apparently seemed like such an obvious good idea, it became standard medical advice without first being tested . Monthly self breast exams, yearly clinical breast exams (CBE) and regular mammograms after a certain age have been longstanding major components of breast cancer screening in the US.

Increasingly in medicine, we are trying to figure out which of our screening practices actually work. In the US, it would be very difficult to study SBE as a primary screening test, in the absence of CBE and mammograms.  So studies on the effectiveness of SBE have come from countries where other breast cancer screening is not readily available.

A major study on SBE, conducted in China, involved 266,064 women, half of whom were repeatedly instructed in SBE and reminded to do the exams. None of the women had access to CBE or mammograms.

After 10 to 11 years of followup, the women who did SBE had the same breast cancer mortality as the control group. The main difference between the two groups was the SBE group had twice as many benign breast biopsies.  A smaller study in Russia also showed no measurable SBE benefit.

On the face of it, these results seem contrary to many women's experience, as a fair number of breast cancers are found by women themselves.

Sometimes women examine their breasts because some life event made them worry in particular about breast cancer. Or, they became aware that their breast looked or felt different and then they did a self exam. Only rarely does one of my patients tell me she found a worrisome lump while doing her regular exam.

SBE every month is much too often to note meaningful change. Even if an area contains breast cancer, it is unlikely to feel different from one month to the next.  Perhaps women themselves intuitively have always known this, as the majority have never done monthly exams.

The USPSTF agrees with what most women actually don't do and recommended against SBE for women at average risk for developing breast cancer.

For women at high risk for breast cancer, SBE appears to be more helpful. At the 2009 American Society of Breast Surgeons annual meeting, a small study found high risk women doing SBE every six months were as accurate as annual mammograms and MRIs in identifying breast cancers.

Being well-trained in SBE may be particularly important for younger high risk women who have not yet begun screening with mammograms.

And what about the clinical breast exam? The USPSTF found no evidence that CBE by itself reduces breast cancer mortality.   

In the US, most women who have regular clinical breast exams also have access to mammograms. It would be difficult, probably ethically impossible, to do a large study of CBE as a stand alone screening test.

Physicians consider breast exams to be an important part of a woman's annual physical. Yet, many physicians could approach breast exams in a more thorough, systematic way. An optimal CBE takes at least one minute per side, with the entire breast being systematically evaluated. Ideally, visual inspection is also done.

If all clinicians perfomed CBE in a more structured, standardized manner, the effectiveness of CBE, though difficult to measure, would almost certainly improve.

So what are women to do? Women at high risk for breast cancer may benefit from learning to do SBE and doing an exam periodically. A six month interval seems reasonable and has a little data to back it up. Women at average risk should be aware of changes in their breasts and seek medical advice about persistent changes.

And all women who have their breasts examined by a medical professional should get the potential benefit of a thorough exam.

Reducing breast cancer risk

Last time, I wrote about using the Gail model and breast density on mammogram to estimate individual risk of developing breast cancer. Now, I'd like to address how we can reduce risk of developing breast cancer.

There are three main ways to reduce that risk — surgical intervention, medication and lifestyle modifications.

The surgical approach, prophylactic mastectomy, is a reasonable option for women at extremely high risk for breast cancer, such as those who carry a BRAC mutation. Women with a strong family history of breast cancer should consider genetic counseling to discuss testing for this mutation.

The majority of breast cancers, however, are not linked to the BRAC mutation. For women at average or moderately increased risk, other risk-reducing interventions are appropriate.

The FDA has approved two medications — tamoxifen and raloxifene — to reduce breast cancer risk in higher risk women. Both of these meds are selective estrogen receptor modulators (SERMs). They act like an estrogen in some tissues and block estrogen action in other tissues. Both act like an anti-estrogen in breast tissue.

Tamoxifen has been approved since 1998 for both pre- and postmenopausal women with a Gail model five year risk of developing breast cancer of greater than 1.7%  Tamoxifen use for five years can reduce breast cancer risk by about 40%.

Tamoxifen has not been widely prescribed for eligible women, mostly because of adverse effects. Because tamoxifen acts like an estrogen in endometrial tissue, it increases risk of endometrial cancer. It also increases hot flushes and thromboembolic events. Many primary care physicians are not personally familiar with tamoxifen and are not comfortable prescribing it.

Raloxifene, recommended for postmenopausal women only, also reduces breast cancer risk by at least 40%. Raloxifene may gain wider use, as physicians have also prescribed it for osteoporosis, and it does not increase risk of endometrial cancer. Raloxifene has other adverse effects similar to Tamoxifen.

Researchers are actively working on the next generation of SERMs, hoping to create the perfect combination of estrogenic and antiestrogenic effects. In the meantime, higher risk women and their physicians have to consider risk vs benefit in deciding whether to use one of today's SERMs.

Lifestyle changes can reduce breast cancer risk and be adopted by women at all levels of risk. Getting regular exercise, maintaining a normal weight, and minimizing alcohol intake appear to reduce risk in most studies. If you are sedentary and overweight, this is another reason to get serious about exercise and weight loss.

The Gail model is most accurate predicting risk of estrogen receptor positive (ER+) breast cancers — SERMs and lifestyle changes are effective in reducing risk of this type of cancer. The majority of breast cancers are ER+.

So far, we do not have a good model for predicting ER- breast cancer and few strategies, other than surgery, for preventing it. Understanding receptor negative breast cancer is a challenging area of  breast cancer research.

 

Predicting breast cancer risk

When women 40 and older come to clinic for an annual exam, one of the things I like to know is their risk of developing breast cancer. We use the Gail model to estimate a woman's risk of developing breast cancer over the next 5 years and during her lifetime. The model also compares individual risk to the average risk of women the same age.

While the Gail model isn't perfect, it does help us identify women at greater than average risk so we can discuss options for reducing their risk. I'll discuss those options soon — for now, I want to focus on breast cancer risk assessment.

The Gail model takes into account breast cancer in first degree relatives, as well as age of starting menstruation, current age, age at first child's birth, race and breast biopsy history.

Other factors, not included in the model, do modify breast cancer risk. Extended breastfeeding, regular exercise and abstaining from alcohol appear to reduce risk. Use of estrogen and progestin hormones postmenopausally or breast cancer in several second degree relatives, such as a grandmother or aunt, may increase risk.

Women whose family histories include several cases of breast cancer, or related ovarian and colon cancers, should consider genetic counseling. Their family may have a genetic mutation, BRAC1 or BRAC2, that significantly increases risk of developing these cancers. 

For most women, risk assessment from the Gail model gives us a starting point, and we keep other factors in mind as the model may overestimate or underestimate an individual's risk.  The Gail model predicts risk more accurately for breast cancers that are estrogen receptor positive.

A recent study suggests estimating breast cancer risk is clearly worthwhile. The researchers also confirm earlier reports that breast density on mammogram importantly affects breast cancer risk and should be included in risk assessments.

On mammograms, glandular and connective tissue appears white, or radiodense, and fatty tissue appears black, or radiolucent. When radiologists interpret a mammogram, they usually include a comment about breast density. Breasts with the least density contain less than 25% fibroglandular tissue, whereas very dense breasts have more than 75% fibroglandular tissue.

Women with very dense breasts have approximately four times the risk of developing breast cancer as women with minimal breast density.

Most women don't know what their mammographic breast density is, because that information is usually not included in letters to patients from the mammogram facility.  You can ask your doctor what the physician's report says about your breast density. 

Our biggest risks of developing breast cancer are being female and getting older. But information from models and mammograms can be used to estimate an individual's risk.

The Gail model could be improved if mammographic breast density were included in its risk assessment.Other models have been developed that include breast density, but they are not as accessible as the Gail model.

Once we have identified women at higher risk of developing breast cancer, we can take steps to reduce that risk.  I'll write about breast cancer risk reduction next time.

HRT and breast cancer - relative risks vary with the progestin

One of the newer pieces of information in the HRT puzzle is that risk of invasive breast cancer varies according to the progestin used.

A progesterone or synthetic progestin protects the uterine lining from overstimulation by estrogen that can lead to endometrial cancer. Women who've had a hysterectomy can safely take estrogen alone.

In a recent editorial, Dr Robert Barbieri summarizes some of the latest scientific information that might change how we prescribe hormones for menopausal women.

Ideally, we want to protect the lining of the uterus without adding to other risks. We do not yet have that ideal agent, but it's becoming clear there are different risks with the hormones that are currently available.

Combined information from a  French study and a German study, shows progesterone use minimally affected breast cancer risk. In the US, the only progesterone currently approved for endometrial protection is Prometrium.

With medroxyprogesterone, used in PremPro and as a separate tablet, the relative risk of breast cancer was 1.48. Norethindrone had the highest relative risk — 2.11.  Norethindrone is found in FemHrt, Activella, Combipatch and as a separate tablet.

It also appears using a progestin cyclically, rather than every day, carries less breast cancer risk because less progestin is used.

Continuous hormone regimens with daily estrogen and progestin were developed so women could avoid having period-like withdrawal flow. Now, with women taking HRT for a shorter time after menopause, avoiding withdrawal flow should be less of an issue.

For various reasons, some women do stay on postmenopausal HRT for longer than the 3-4 years now recommended.  For women on HRT for an extended time, it is especially important to update HRT regimens using our best information on risks and benefits.

Up next will be the safest way for postmenopausal women to take estrogen.

When does breast cancer risk increase with postmenopausal hormone use?

Most medical experts agree menopausal women on estrogen and progestin hormones for an extended time have an increased risk of developing breast cancer. The Women's Health Initiative (WHI) clinical trial was halted in 2002 after 5.2 years because increased breast cancer risk was found.

Yet some women have severe menopausal symptoms and can benefit from being on hormone replacement, at least for a time.

How long can women take combination hormones before breast cancer risk increases? Two recent reports address this question.

A Finnish report using national registry data involved 221,551 women on combination hormones for varying periods of time. Women taking hormones all received the same estrogen — estradiol — but were on a variety of progestins.

A progestin is used so the uterine lining is not overstimulated by estrogen.

They were divided into groups based on how long they took the hormones. The incidence of breast cancer in combination hormone users was compared to that of age-matched women in the general population.

For women using combination hormones up to 3 years there was no increased risk of breast cancer. After 3 years, increasing risk was noted with longer use. Women using hormones for longer than 10 years had the highest risk. 

Risk also varied according to type of progestin and whether the progestin was taken intermittently or continuously.  I will look at this topic in a later post.

A Boston University study also looked at when breast cancer risk increases with estrogen and progestin use. This study compared 4, 515 women with breast cancer to 18,058 age-matched women who had not been diagnosed with breast cancer.

These researchers found risk with estrogen and progestin use increased after 4 years. This study also looked at estrogen and testosterone combinations and found no increased risk over time unless a progestin was also used.

After the WHI results, most physicians have advised menopausal patients to take combination hormones for less than 5 years.  It now appears we should be even more conservative, as breast cancer risk may start rising after 3 to 4 years of hormone use.

The good news is women may be able to use estrogen and progestin hormones for a few years after menopause without adding to their breast cancer risks.

Breast cancer risk decreases after stopping hormone replacement

We've been down a long and winding road trying to understand how best to approach hormone replacement therapy (HRT) after menopause. The road's direction changed dramatically when results from the Women's Health Initiative (WHI) were first released in July of 2002. 

Prior to the WHI, less rigorous studies had suggested replacing female hormones for an extended time after menopause benefited most women. It appeared that a possible increased risk of developing breast cancer was more than offset by significant protection against heart disease.

The initial WHI results contradicted that, especially for women taking both estrogen and a progestin during the 5.2 years of the study. Compared to women on placebo, combination hormone users had a definite increased risk of developing breast cancer and got no extra protection against heart disease.

Risks for women on estrogen alone are different — this post addresses only combination HRT including estrogen and a progestin. (Some women take both because a progestin protects the lining of the uterus from overstimulation by estrogen. Women who've had a hysterectomy can take estrogen alone.)

After the WHI, physicians prescribed HRT less often and many women discontinued use on their own. Breast cancer rates dropped in the US, starting In 2003 and continuing through 2005.

A new report from the WHI investigators suggests the decline in US breast cancer is almost certainly due to decreased use of combination HRT.  An earlier, alternate explanation, that lower mammography rates led to fewer diagnoses, appears not to be true.

The WHI results suggest a woman's breast cancer risk returns to baseline approximately 2.5 years after stopping combination HRT.

The WHI was a very large, well-designed study that has held up under prolonged scrutiny.  While only one type of estrogen and progestin was used in the clinical trial, increased breast cancer risk has also been found with other combination HRT regimens. It does appear that a progesterone may be safer than synthetic progestins, and that different progestins have different levels of risk for breast cancer. I'll look at those differences in future posts.

Why is combination HRT still prescribed? Some women have severe menopausal symptoms, mainly frequent hot flushes, that can effectively be addressed only with hormones. However, we now recommend the lowest possible dose of HRT for the shortest possible time.

HRT is a complicated topic that I will discuss frequently as new information becomes available. Later this week, I'll review a Finnish study that looked at how soon breast cancer risk increases with combination HRT use.