Warning Signs

While the aforementioned patient’s symptoms can point to any number of conditions, there are clues that suggest the possibility of something serious.

“When symptoms are persistent, new, and above and beyond your baseline experience of these symptoms, it’s time to see your primary care doctor or gynecologist,” says gynecologic oncologist, surgeon, and researcher Sanaz Memarzadeh, MD, PhD, UCLA Division of Gynecologic Oncology.

Defining and Diagnosing Ovarian Cancer

The ovaries consist mainly of three types of cells: epithelial, germ, and stromal cells. Each of these cells can form a different type of tumor that may or may not become cancerous. The term carcinoma describes a category of cancer that develops from epithelial cells that line various organs and structures, including the ovaries/fallopian tubes, prostate, liver, and kidneys. Carcinomas are the most common type of cancer. Up to 90 percent of malignant ovarian cancers are carcinomas, and many likely arise from the fallopian tube.

The Value of Genetic Testing

An extensive family history of ovarian and breast cancer is a good reason for genetic testing. BRCA1 and BRCA2 gene mutations are most often associated with breast cancer, but they also predispose patients to ovarian cancer. It is estimated that about 44 percent of women who inherit a BRCA1 mutation and about 17 percent of women who inherit a BRCA2 mutation will develop OC by the age of 80.

If a woman diagnosed with epithelial OC has not been genetically tested, Dr. Memarzadeh says there is value in doing so.

“If a patient has a BRCA mutation, there could be increased risk for other types of cancer, such as melanoma, breast, and pancreatic,” she says. “Because the mutation is hereditary, there are implications for siblings and children. There is a 50 percent chance of passing the gene on to children. Genetic testing also informs treatment. For example, PARP inhibitors have been shown to arrest the growth of cancer cells when a BRCA mutation is present. These drugs have been helpful in both maintenance therapy and for recurrent cancer in patients with BRCA-associated ovarian cancer.”

PARP inhibitors are among the most exciting and newer therapeutic treatments. Advances such as these enable physicians to treat according to a patient’s genetic make-up. New treatments get their start in basic science labs, such as the G.O. Discovery Lab (www.godiscoverylab.com) founded by Dr. Memarzadeh. She, her team, and collaborators at UCLA are in the pre-clinical phase of targeting mutant p53 protein, which results from genetic changes commonly seen in ovarian and other cancers.

“It plays a central role in initiating epithelial ovarian cancer, and there is evidence to suggest it induces resistance to standard chemotherapies, such as carboplatin,” explains Dr. Memarzadeh. “We are working to restore the normal function of mutant p53 protein with the hope of reinstating sensitivity to chemotherapy in a subset of tumors.”

Advancing Surgical Treatment

Surgery to remove the ovaries is the go-to preventive strategy upon discovery of a genetic mutation. Once diagnosed with OC, surgery has also been the traditional first course of treatment. But evolving data show that patients who have extensive disease difficulties may benefit when chemotherapy is used to shrink the tumor and then surgically remove it. After surgery, chemotherapy usually entails a combination of drugs meant to destroy any remaining cancer cells. In some cases, Dr. Memarzadeh says she has had successes with chemotherapy as the first course of treatment, and recommends individualizing treatment for each patient.

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But in the past 30 years, deaths from cervical cancer have been cut in half, due primarily to screening tests and preventive health examinations, the American Cancer Society (ACS) reports. Still, more than 4,000 women die from the disease each year, according to the ACS. So before you develop any cervical cancer symptoms—and to prevent the disease in the first place—talk to your doctor about periodic gynecologic exams and whether you should be vaccinated against a common cause of cervical cancer.

Signs of Cervical Cancer

Cervical cancer generally begins as changes to the cells lining the cervix, the lower portion of the uterus. Oftentimes, these precancerous cells go away on their own, but in some women they develop into dangerous invasive cancers. Although the transformation from precancerous cells to invasive cervical cancer usually takes place over several years, it can occur more rapidly, in less than a year.

Most women do not experience cervical cancer symptoms until the disease has advanced. By then, the cancer may have spread deeper into the cervix, uterus, and other nearby tissues. The most common cervical cancer symptoms include:

• Irregular vaginal bleeding: Abnormal bleeding between periods, longer/heavier menstrual periods, postmenopausal bleeding, or bleeding after sexual intercourse or a pelvic exam.
• Painful intercourse.
• Abnormal vaginal discharge: Unusual discharge of vaginal fluids; may be brownish or contain some blood; may occur between periods or after menopause.

Although these problems may be signs of cervical cancer, they also may be symptoms of other medical conditions, such as an infection. These warning signs warrant an immediate visit to your doctor.

Early Detection a Must

Cervical cancer is curable if found early. But once the cancer progresses, the prognosis worsens, and the likelihood of a cure diminishes.

Fortunately, these days doctors find precancerous changes in the cervix much more commonly than they do invasive cervical cancer. Regular screening with the Pap test has allowed for earlier detection and treatment of these cellular changes before cancer develops. The Pap test involves a swab of the cervix to remove cells for examination under a microscope. Your doctor also may order a test for human papillomavirus (HPV) along with the Pap test.

The ACS and other medical organizations recommend that women begin cervical cancer screening at age 21, along with these other recommendations:

• Women ages 21 to 29 should undergo a Pap test every three years. (HPV testing is not recommended for these women unless they have abnormal Pap test results.)
• Women ages 30–65 should have “co-testing” with a dual Pap/HPV test every five years, or a Pap test alone every three years.
• Women over age 65 with no previous abnormal screening results should not be screened.

However, those with a history of abnormal cervical changes should continue screening for at least 20 years after precancerous cells were found.

• Women who have had a total hysterectomy no longer need screening, unless the procedure was done to treat cervical cancer or a precancerous lesion.
• Women at higher risk of cervical cancer—such as those with a weakened/suppressed immune system, a history of cervical cancer or precancerous cervical lesions, or women whose mothers were given the hormonal drug diethylstilbestrol (DES) to prevent miscarriage—may require more frequent screening.

If your screening tests are abnormal or you have suspected cervical cancer symptoms, your doctor will order a colposcopy, a detailed examination of the cervix. Any suspicious areas will be biopsied to confirm a diagnosis.

Note that just because guidelines do not recommend yearly Pap tests, that doesn’t necessarily mean you should abandon your annual gynecologic examinations. Talk to your physician about the importance of these exams.

Know Your Risk and Reduce It

Several factors increase your odds of developing cervical cancer, such as smoking, a weakened immune system, becoming pregnant before age 17, obesity, and having a mother or sister who had cervical cancer.

However, infection with HPV is the most important risk factor for cervical cancer. HPV encompasses more than 150 viruses and can be transmitted during sex or skin-to-skin contact. HPV infections are fairly common, and in most cases the immune system simply clears the infection. But in some cases, the infection persists and may cause cervical cancer and other malignancies.

Avoiding activities that increase exposure to HPV, such as having sex at a younger age or having many sex partners, may help reduce your risk of HPV infection and, potentially, cervical cancer.

Also, talk to your doctor about the HPV vaccine, which consists of three injections given over six months. The vaccine can protect against new, but not existing, HPV infections, so to offer the most protection, it should be given before you become sexually active.

The ACS and the U.S. Advisory Committee on Immunization Practices recommend the HPV vaccine for girls ages 11 to 12, and it may be considered for girls as young as age 9. The ACIP recommends “catch-up” vaccinations for women ages 13 to 26 who haven’t already received the HPV vaccine; the ACS recommends these catch-up vaccinations for girls up to age 18, while those ages 19 to 26 should talk to their doctor about their HPV risk and whether they still need the vaccine.

For related reading, please visit these posts:

• HPV-Related Throat Cancer on the Rise Among Men
• Uterine Cancer Symptoms Can Lead to Early Diagnosis
• What Is Acidophilus and What Are Its Benefits?
• Respond Quickly to Ovarian Cancer Symptoms
• Ovarian Cyst Symptoms: How They Develop, How to Treat Them

This article was originally published in 2016. It is regularly updated. 

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Older adults reduced their risk factors for heart disease and stroke between 1990 and 2010, according to a new study (Aging and Clinical Research, March 22). The study used National Health and Nutrition Examination Survey data on adults age 40 and older to estimate total cardiovascular risk, the prevalence of individual risk factors, and potential factors contributing to changes in risk. Researchers compared measures for these risks on three dates about 10 years apart. The measures included systolic (upper number) and diastolic (lower number) blood pressure, body mass index (BMI), total cholesterol, HDL (“good”) cholesterol, LDL (“bad”) cholesterol, triglycerides (fats that circulate in the blood) and blood glucose. The analysis showed that both men and women decreased their mean number of cardiovascular risk factors, with the greatest improvement among those aged 60 to 69. While men showed steady improvement over the two decades, women’s gains occurred in the latter portion, from 2000 to 2010. It is likely that decreased rates of smoking played a role in these improvements, along with increased use and efficacy of prescription medications that control high blood pressure and cholesterol.

Opt for Fruit Instead of Fruit Juice

Many of us see fruit juice as healthy because of its vitamin and mineral content. But it’s also high in sugar that won’t do your weight any favors, according to a recent study (Preventive Medicine, April). The data showed that adding one 6-ounce serving of 100 percent fruit juice daily was associated with a weight gain of 6.4 ounces over a period of three years. Conversely, increasing the amount of whole fruit intake by one serving per day resulted in a weight loss of about 15 ounces over three years. The findings may reflect the fact that the sugar in whole fruit is balanced by its fiber content, so try to choose whole fruits over fruit juice whenever possible. 

Statin Compliance

Many people with an elevated risk for cardiovascular disease (CVD) stop taking cholesterol-lowering statins because they don’t believe they need the drugs, according to a Mount Sinai study presented at the American College of Cardiology Scientific Sessions in March. Of the 7,216 study participants who had been prescribed statins, 15 percent discontinued the drug because of a perceived lack of need. Statins are highly effective when it comes to lowering the risk for CVD-related events and mortality, so don’t stop taking yours without discussing the decision with your doctor. Also tell your doctor if side effects like muscular aches and pains are affecting your compliance with the drug, since a different medication or a lower dose could solve the problem.  

Ovarian Cancer Screening 

An updated recommendation from the U.S. Preventive Services Task Force (USPSTF) reiterates its recommendation against screening for ovarian cancer in low-risk women without symptoms. The USPSTF reviewed evidence on the benefits and harms of screening in asymptomatic low-risk women, and found evidence that it does not reduce ovarian cancer mortality. It also found that the harms from screening are at least moderate, and may be substantial in some cases. The recommendation reflects the fact we don’t yet have effective screening methods for ovarian cancer. The tests we do have are susceptible to false positive results that may lead to unnecessary surgery, and also can give a false negative result that causes women to ignore ovarian cancer symptoms. The USPSTF recommendation doesn’t apply to women who are high risk for ovarian cancer (for example, women with a personal or family history of breast and/or ovarian cancer, and those with a genetic mutation such as BRCA-1 or BRCA-2). The updated recommendation was published in the Journal of the American Medical Association, Feb. 23.   

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A Constellation of Different Cancers Ovarian cancer should not be categorized as a single disease, but rather as a constellation of different cancers, according to a 2016 report from the National Academies of Sciences, Engineering, and Medicine (NASEM). The report emphasized that while progress has been made in ovarian cancer research over the past few decades, much remains to be learned. It also pointed to evidence suggesting that many ovarian cancers begin in other tissues (for example, the fallopian tubes), and then metastasize to the ovary, or arise from cells that are not considered intrinsic to the ovary. “Presently, researchers don’t have a complete understanding of how each subtype of ovarian cancer progresses,” Dr. Bloom notes. “This information could help when it comes to developing more accurate screening tests.”

Getting Screened The U.S. Preventive Services Task Force recommends against routine screening of asymptomatic women for ovarian cancer because screening has not been shown to substantially reduce deaths from the disease. Moreover, the current methods of screening—transvaginal ultrasound and/or a blood test—are not sensitive enough to reliably screen for ovarian cancer. “Transvaginal ultrasound tends to detect cancers that are already advanced,” Dr. Bloom explains. “The blood test measures levels of an ovarian cancer marker called CA-125—but about 20 percent of women with ovarian cancer don’t have elevated CA-125 levels, while about three percent of women who do have high levels don’t have ovarian cancer, since CA-125 also can be raised by other conditions.”

Unreliable testing raises the risk for inaccurate results that may have serious consequences. “Women who get a false-positive result may undergo further invasive tests, and unnecessary surgery,” Dr. Bloom says. “Conversely, women who get a false-negative when cancer is in fact present may not mention any symptoms to their doctor because the test gave them an ‘all-clear.’ This could mean it is too late to successfully treat the disease when it is finally diagnosed.”

Numerous online tests that claim to screen for ovarian cancer are available—however, in September 2016, the Food and Drug Administration announced that these are not reliable and should not be used.

What if You’re High-Risk? The USPSTF recommendation against routine screening doesn’t apply if you’re high risk for ovarian cancer. This category includes women who have a family or personal history of ovarian and/or breast cancers, or a genetic mutation such as BRCA-1 or BRCA-2—if you fall into these categories, discuss with your doctor whether you should be screened for ovarian cancer.

Know the Symptoms Given that most women who develop ovarian cancer don’t have an inherited gene mutation or a significant family history of the disease, the NASEM report called for the identification and evaluation of a range of potential risk factors for ovarian cancer, in addition to genetics. There already is some evidence that obesity may raise ovarian cancer risk, along with long-term use (more than five years) of hormone replacement therapy. Diet also could be a factor, with research suggesting that women who follow a low-fat diet are less susceptible to the disease. Two 2016 studies implicated lack of exercise. In one, women who reported never having engaged in recreational physical activity were 34 percent more likely to develop ovarian cancer than those who exercised regularly. The second study found that women with ovarian cancer who were inactive in the years before their diagnosis were 22 to 34 percent more likely to die from the disease than women who had done at least some regular exercise.

The NASEM hopes that researchers can come up with a risk assessment tool that accounts for the various ovarian cancer subtypes, as well as early detection strategies that go beyond current imaging technologies and biomarkers. Until then, and without reliable screening methods, your best protection against ovarian cancer is to be aware of the symptoms that can red-flag the disease. “While ovarian cancer symptoms are vague enough to be mistaken for signs of a less severe gastric problem, what does differentiate them is that they tend to increase in frequency if cancer is present,” Dr. Bloom says. “If you experience symptoms every day over the course of a month, mention them to your doctor.”  

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That’s because ovarian cancer symptoms tend to be nebulous, easily mistaken for other, more common problems. Nevertheless, it’s critical not to ignore them. Seeking prompt medical help for potential symptoms of ovarian cancer is your best chance to receive treatment that may save your life.

Ambiguity in Ovarian Cancer Symptoms

Only about one in five ovarian cancers is discovered at an early stage, according to the American Cancer Society (ACS). By the time a gynecologist can feel an enlarged cancerous ovary during a pelvic exam, the cancer is usually advanced. Plus, screening tests—such as transvaginal ultrasound and blood tests for a protein (CA-125) that’s elevated in many women with ovarian cancer—have not proven successful at preventing deaths from the disease.

So, it’s vital to acknowledge any signs of ovarian cancer and report them to your doctor. The disease may cause changes in urinary habits, such as feeling like you have to urinate all the time or more frequently. You also may experience bloating, feeling full quickly when you eat, and abdominal or pelvic pain or pressure. These more common warning signs may be accompanied by other symptoms of ovarian cancer, including pain during intercourse, fatigue, back pain, menstrual changes, abdominal swelling, and stomach upset.

Although early-stage ovarian cancer may cause symptoms, these warning signs are more likely to develop after the disease has spread beyond the ovaries. Compounding the problem is that once you experience these symptoms, they’re more likely to be a result of other medical problems, including several benign conditions and certain other cancers.

For example, ovarian cancer symptoms may be easily mistaken for signs of a digestive disorder. As such, you might visit your primary care physician or see a gastroenterologist without considering that the problem originates in your gynecologic system. Consequently, in many women a diagnosis of ovarian cancer (and treatment for the disease) is often delayed. This delay may partly explain why ovarian cancer is the fifth-leading cause of cancer death among women and accounts for more deaths (about 14,180 a year) than any other gynecologic cancer, according to the ACS.

Sometimes, but not always, the symptoms are more severe when ovarian cancer is the cause. Ovarian cancer symptoms tend to be continual and mark a change from how you normally feel (e.g. the symptoms are new, occur more frequently, or increase in severity). The ACS recommends that you see a doctor—preferably a gynecologist—if you experience signs of ovarian cancer almost daily for a few weeks or more, or more than 12 times a month, and these symptoms can’t be explained by other medical conditions.

Recognize Your Risk

The risk of ovarian cancer rises after menopause and with age, peaking in a woman’s 70s. The disease is more common among Caucasians than African-Americans.

Women who are obese, have a history of breast cancer, or have taken estrogen alone (without progesterone) after menopause appear to be at higher risk of ovarian cancer, research suggests. On the flip side, the odds of developing the disease may be lower in women who have taken birth control pills, have undergone tubal ligation (had their “tubes tied”) or a hysterectomy, or have been pregnant and carried the child to term before age 26, the ACS notes.

Your risk of ovarian cancer is also higher if a first-degree relative (mother, sister, or daughter) has had the disease, and the risk increases with each additional relative diagnosed with ovarian cancer. Researchers also have identified a link between ovarian cancer risk and a family history of colorectal and breast cancer.

As many as one in 10 ovarian cancers may be attributable to inherited cancer syndromes. One of these syndromes is caused by mutations in the BRCA1 and BRCA2 genes, which have been associated with increased risk of cancers of the ovaries, breast, pancreas, and prostate. While an average woman faces a 2 percent lifetime risk of developing ovarian cancer, the risk is 35 to 70 percent for women with BRCA1 mutations and 10 to 30 percent by age 70 for women with BRCA2 mutations, according to the ACS.

If you have a strong family history of ovarian or breast cancer, talk to your doctor about testing for BRCA mutations. If you test positive for BRCA, talk to your gynecologist about ovarian cancer screening. Your gynecologist might discuss having your ovaries removed if you no longer plan to have children.

Originally published in May 2016 and updated.

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Hard to Detect

Ovarian cancer is one of the hardest cancers to detect for a combination of reasons. “The cancer has to be fairly advanced for doctors to feel any abnormality during a physical examination,” says Monica Prasad-Hayes, MD, assistant professor of obstetrics, gynecology and reproductive science at Mount Sinai. “By the time a cancer enlarges the ovary to the extent its size is considered abnormal, the cancer will likely have spread. Another factor that can delay diagnosis is that ovarian cancer symptoms—which include bloating, pelvic pain, low back pain, increased urinary frequency, constipation, and lethargy—are nonspecific, and can easily be mistaken for signs of a less serious problem.”

Effective Treatment Vital

Better ovarian cancer survival for older women depends on an effective treatment regimen. This is the focus of a recent study (Obstetrics & Gynecology, January) led by Jenny Lin, MD, associate professor of medicine at Mount Sinai. Dr. Lin and her colleagues examined trends in treatment and overall survival for 7,938 women age 65 and older, with stage III and IV ovarian cancer. Overall, 2.9 percent of the women received no treatment, and 15.4 and 24.8 percent respectively underwent debulking surgery to remove as much as possible of the tumor, or chemotherapy alone, while 41.8 percent underwent surgery and chemotherapy in an optimal time frame (called optimal treatment). In addition, 15.1 percent of women underwent surgery and chemotherapy, but either the timing was not optimal or they did not complete their chemotherapy.

The longest survival time—39 months—was seen in women with optimal treatment. However, the data also showed a decrease in the number of women who received optimal treatment over the last decade. “It isn’t entirely clear why there has been a decrease,” Dr. Lin says. “It is possible doctors are being more selective when it comes to recommending optimal treatment—you have to be well enough for surgery and chemotherapy.”

The study also found that survival was similar for those who underwent surgery only versus no treatment, but better overall survival (14.4 months) was seen for those who received chemotherapy only. “In the U.S., surgery is typically performed prior to chemotherapy,” says Dr. Lin. “These data suggest that we maybe need to offer chemotherapy first to women who aren’t in good enough health for surgery.”

Survival Boost?

A study published in the September 2015 issue of Obstetrics & Gynecology offers hope for women with advanced disease, suggesting that the 10-year survival rate is higher than previously thought, even in women with factors that have previously been associated with a poor prognosis, such as older age. Researchers analyzed data on 11,541 women who had been diagnosed with ovarian cancer: of these women, 3,582 (31 percent) survived for 10 or more years after their diagnosis. The survivors included 954 women who had a poor prognosis because they were older at the time their cancer was detected, and/or had higher-grade tumors, which grow faster and are more likely to spread.

It isn’t clear what impacted survival in the study—further investigations will aim to clarify this—but Dr. Prasad-Hayes points to treatment advances as a possible factor. “Surgical techniques are better, and we have better drugs and more effective methods of administering them,” she explains. “A combination of intravenous and intraperitoneal chemotherapy, which is given via the abdomen, has been shown to improve survival.” It is important to note, however, that side effects such as abdominal pain, nausea, and vomiting are often more severe with intraperitoneal chemotherapy than with intravenous chemotherapy alone. Because it can be so toxic, women must have normal kidney function and be in good overall health to have intraperitoneal chemotherapy.

What About Screening?

Another recent study (The Lancet, Dec. 17, 2015) suggests that ovarian cancer screening may be more effective than previously thought. Researchers tracked 200,000 women across 14 years: ovarian cancers were diagnosed in 630 who had no screening, 314 of those screened by ultrasound only, and 338 of those undergoing blood tests (which check levels of an ovarian cancer marker called CA-125) and ultrasound. Compared with the group that had no screening, from years 0-14 mortality was reduced by 15 percent among those screened by ultrasound and blood tests, and by 11 percent for those screened by ultrasound only. When women who were found to have undiagnosed ovarian cancer on joining the trial were excluded, the average mortality reduction became 20 percent overall, and 28 percent in years seven to 14.

Presently, the U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for ovarian cancer. It reached this decision after a review of studies showed that screening with ultrasound and blood tests doesn’t reduce the number of deaths from the disease. Transvaginal sonograms are sensitive for the detection of ovarian cancer, but many of the tumors are already advanced when they are detected. As for the CA-125 test, levels of this marker can be elevated for other reasons, including many benign gynecologic conditions. However, Dr. Prasad-Hayes thinks these new data are important. “It took seven years before a significant impact was seen, but even so, these findings may change how we monitor patients in the future,” she observes. For now, keep in mind that the USPSTF guideline doesn’t apply if you are at high risk for ovarian cancer—if you fall into this category, talk to your physician about whether you should be screened.

Guarding Against Ovarian Cancer

Dr. Prasad-Hayes says it is vital to know your risk factors for ovarian cancer, and to recognize symptoms that might indicate you have the disease. Factors that increase risk include certain gene mutations, a personal history of breast cancer or a family history of ovarian cancer, being over age 45, and obesity. Early warning signs for the disease include bloating, pelvic or abdominal pain, feeling full quickly when you eat, low back pain, increased urination, and changes in bowel habits. “These symptoms are vague enough to be mistaken for signs of a less serious gastric problem, but what does mark them out is that they tend to become more frequent if ovarian cancer is the cause,” Dr. Prasad-Hayes says. “If you experience a combination of these symptoms on a daily basis over the course of a month, you should see your doctor.”

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