Watching Women's Health

Does recognizing symptoms lead to early diagnosis of ovarian cancer?

I wrote earlier about the difficulties of diagnosing early ovarian cancer by routinely screening asymptomatic women at average risk for this disease. But what if physicians did a better job of screening women with symptoms linked to ovarian cancer? Could we make the diagnosis at an earlier, more treatable stage?

A recently published study looked at these questions. 

813 women with ovarian cancer (including 212 diagnosed in an early stage) and 1313 otherwise similar women were interviewed about symptoms they experienced before their date of diagnosis (or comparable date for the control group).

Symptoms included early satiety, bloating, abdominal or pelvic pain and urinary changes. A woman was considered symptomatic if she had new onset of any of these symptoms in the year before diagnosis, with symptoms occurring daily for at least a week.

Women who had been diagnosed with ovarian cancer were 10 times more likely than women in the control group to report having had at least one of these symptoms. However, most women reported having symptoms for a relatively short time before diagnosis, regardless of whether their cancer was found in an early or late stage.

(One limitation of the study is that it relied on accurate recollection of symptoms. And, women with a cancer diagnosis may recall symptoms differently than the control group.)

Like other current screening approaches for ovarian cancer, the authors' symptom index had a low positive predictive value. Using their approach, 100 symptomatic women would have to be evaluated to identify one woman with early ovarian cancer.

The other 99 women would undergo ultrasounds, blood work and in some cases, unnecessary surgery, looking for a disease they did not have. At the same time, women who had early ovarian cancer but no symptoms, would not be recognized.

The editorial accompanying the article concludes

Importantly, these findings remind us that wide recognition of symptoms alone will not incrementally improve the overall survival from ovarian cancer. Rather, they highlight the urgent need to develop better molecular markers and improved imaging modalities for ovarian cancer screening. The recognition of specific symptoms associated with ovarian cancer has value. However, to truly affect the cure of ovarian cancer, we need better diagnostic tools for asymptomatic women.

Next, I'll look at what we know about inherited susceptibility to ovarian cancer.

First gyn visit — not so scary for today's teens

When I was an ob/gyn resident in the 1980's, our program provided care at a community teen clinic. Young women were mostly seeking cycle control and contraception, usually wanting to start birth control pills. The supervising physician instructed us to do full pelvic exams, including pap smears and rectovaginal exams, even though some of these teenagers were not yet sexually active. The exams were almost always normal.

The teens were very nervous, in some cases, terrified about the exams, and it took determination and courage for them to follow through with their appointments. Our university-based residency saw this "service" as community outreach, but the thoroughness of our approach, standard for that time, was probably a barrier to care for many frightened young women.

Because of new adolescent health care guidelines from the American College of Obstetrics and Gynecology (ACOG), today's teens can expect a much less intimidating first gyn visit. Since most teens are unlikely to have pelvic abnormalities, ACOG says physicians don't need to perform a pelvic exam at a first gyn visit unless an individual's medical history suggests there may be abnormal findings.

Many teens seek cycle control and/or reliable contraception, and oral contraceptives (OCs) are usually a good choice. In most cases, OCs can be safely prescribed after a thorough medical, family and social history, and a blood pressure check.

ACOG now recommends doing a first pap smear at age 21, regardless of a young woman's sexual history. We can screen for chlamydia, a common infection in sexually active young women, with a urine specimen.

The main threats to adolescent health are risk-taking behavior and unhealthy lifestyles. ACOG recommends a first gyn visit for girls aged 13-15, so ob/gyn physicians can back up parents in encouraging good choices. Our clinics then become a safe place for teens to go for reliable information and resources that build the foundation for a healthy adulthood. 

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.

Pap smears and the adolescent

Invasive cervical cancer is very rare in young women 20 and under. Why is that? Sexually active adolescents are at significant risk for exposure to the human papillomavirus (HPV) but their immune systems almost always clear the virus before an invasive cancer can occur. 

In the past, adolescents with low-grade pap smear abnormalities have been over-evaluated and over-treated.  We now know the majority of these low-grade abnormalities in young women will go away on their own. 

Age-based pap smear guidelines help gynecologists avoid treating adolescents too aggressively. In this age group, we now evaluate and potentially treat only high-grade pap smear abnormalities.  We do not evaluate low-grade abnormalities unless they persist for 2 years.  

Treatment of cervical precancer involves destruction or removal of a portion of the cervix.  Even newer treatment methods can lead to preterm delivery in subsequent pregnancies.  Because most adolescents have their reproductive lives ahead of them, it is important to treat only those young women who are at high risk for actually developing an invasive cancer. 

This post completes the series on new pap smear guidelines. (The others were on the test itself, women 30+ and women under 30.) But there is one last thing all women should know — smoking tobacco doubles the likelihood that HPV infection will lead to a significant precancer of the cervix.  So if you are a smoker, add that to the list of reasons to quit.

Pap smears for women under 30

Why don't we routinely test for high-risk HPV when doing paps on women under 30?  There are two main reasons. 

First of all, compared to women 30 and older, many younger women are not yet in a stable relationship and are more likely to be exposed to HPV.

But after HPV infection occurs, and this is the second reason, a younger woman's immune system is more likely to efficiently clear HPV. 

So younger women commonly have transient HPV infections. They may have a series of short-lived infections from different subtypes, but with routine HPV testing, they would appear to be persistently infected. (Right now, we do not do subtype-specific HPV testing, though this may be helpful in the future.)

Persistent HPV infection over several years may lead to cervical cancer. Transient HPV infection does not involve that risk. Routine HPV screening in this age group would result in unnecessary further testing for a lot of young women, significantly adding to the cost and inconvenience of the initial screening test — the pap smear.

We do ask the lab to check for HPV activity if a younger woman has a borderline pap result. If a woman has a borderline pap and tests positive for HPV, we evaluate her further for a cervical precancer. If she has a borderline pap and tests negative for HPV, we know she is at low risk for a precancer and recommend doing the next pap in one year.

Pap smears for women 30 and older

An earlier post introduced new approaches to pap smears.

We have known that the human papillomavirus (HPV) is the cause of cervical cancers and precancers for at least two decades. There are many HPV subtypes and it has taken a long time for researchers to figure out which subtypes are high risk for causing cervical cancers and precancers. Testing individuals for high-risk HPV has been used clinically only in the past 5 years or so.  

The American College of Obstetrics and Gynecology (ACOG) recently released a new practice bulletin based on consensus guidelines for Pap smear and HPV screening.

Because HPV is a common virus, women who have ever been sexually active have up to an 80% lifetime risk of acquiring it. Most women with a healthy immune system will clear HPV or suppress it to harmless levels of activity in a matter of months.

Persistent high risk HPV activity may cause cervical cancer over an average time frame of 8-12 years. Because younger women clear the virus more efficiently, a woman's age plays a role in screening guidelines. In this post I will focus on the screening recommendations for women 30 and over.

We now offer these "older" women a pap with automatic high risk HPV testing. (We don't test for low risk HPV because it does not cause cervical cancer.) If we get a double negative result — a negative Pap and a negative HPV — that individual is at extremely low risk for cervical cancer for an extended period of time. The best research suggests a three year interval before doing the next pap smear. This is still a conservative recommendation given the average length of time it takes for a cervical cancer to develop.

What if the pap is negative but the HPV test is positive?  Then we know that person has a risk of developing a cervical precancer even though the cells look normal on the pap. We do the next pap in one year.  In many cases, the immune system will have cleared HPV during that time.  If not, and HPV is still present, we do further testing for cervical precancers.

So adding an HPV test to the basic pap allows us to identify more accurately which women are at risk for cervical precancers in the next few years and which women are not.  Of course we still want to see you annually for an exam and other screening tests even if you don't need a pap every year.

Why don't we use routine HPV testing in younger women?  I'll explain in my next post.

Chlamydia — On the rise or just better screening?

When I was in my first year of residency in the middle 1980's, one of my fellow residents gave a Grand Rounds presentation called "Chlamydia — Does it Exist?" At that time testing for chlamydia was unreliable and labor-intensive in clinic and the lab. Screening practices varied. We have come a long way since then.

Now we have accurate tests for chlamydia, clear guidelines on who should be screened and a better idea of how common the infection is. The Centers for Disease Control and Prevention (CDC), a federal agency based in Atlanta, recently reported all-time-high rates of chlamydia infection — 370 cases per 100,000 people for 2007. This was a 7.5% increase from 2006.

The CDC suggested the increase may be due to better screening rather than more people actually having the problem. 

Why do we care about chlamydia? Many women and most men have few symptoms from this sexually transmitted disease. The problem is not so much the initial infection as what follows. In women, chlamydia initially infects the cervix. If untreated it can ascend into the uterus and fallopian tubes, possibly causing pain, scarring and infertility [CDC chlamydia fact sheet].

We can easily treat chlamydia with antibiotics for a woman and her partner. 

Because chlamydia is more common in younger age groups, the CDC and the American College of Obstetrics and Gynecology recommend screening all sexually active women 25 and under. We also  screen all pregnant women and women over 25 with possible exposure from new partners.

Today's young women in the age group most at risk for chlamydia are remarkably well-informed but still do not routinely protect themselves.

If your doctor suggests chlamydia screening consider that there are many good reasons to do the screening and few good reasons for skipping it. Chlamydia does exist.

The Pap Smear - How a good screening test keeps getting better

Most people know the pap smear is a screening test for cervical cancer that women should get done annually. In fact many patients view getting their pap smear done as a main reason to come in for an annual exam.

A new American College of Obstetrics and Gynecology practice bulletin describes how, using combined pap smear and human papillomavirus (HPV) testing, some women may safely get pap smears done every three years. Ob/Gyn physicians are now able to identify women at low risk for cervical cancer and precancer more accurately, so we can appropriately screen them less often than women at higher risk.

Both the pap and the HPV test are done from cells collected from the cervix during a speculum exam. The pap smear looks at cervical cells microscopically to see if there are abnormalities suggesting a precancer or cancer. The HPV test checks for activity of the high risk forms of the human papillomavirus that are known to cause precancers and cancers. There are low-risk forms of HPV that we don't test for as they rarely cause cervical cancer.

The American Society for Colposcopy and Cervical Cytology released detailed consensus guidelines for combined pap/HPV testing several years ago. Because these guidelines are complex and mark a departure from the annual pap "gold standard," many physicians have been slow to use them in their practice. It definitely takes some time to explain the new pap smear approach to patients and the new follow-up strategies are more complicated.

The newer guidelines describe a different approach for adolescents, women under 30 and women 30 and older. Age-based guidelines add to the complexity but benefits for women in each age group are clear.

Because this is an important topic, I will devote a series of posts to pap/HPV screening (women 30 and older, women under 30 and special considerations for adolescents). Check here or ask in clinic for information that applies to your age group and personal pap results.