Allie Casey

Findings from a recent pilot study done at the University of Pittsburgh Medical Center showed a potential link between e-cigarette use and bladder cancer.

&ldquo;We&rsquo;ve known traditional smoking raises bladder cancer risk, and given the surge in popularity of e-cigarettes, it&rsquo;s imperative we uncover any potential links to e-cigarette smoke and bladder cancer,&rdquo; said Sam S. Chang, MD, MBA, who moderated the press session during&nbsp;which the study was presented at the American Urological Association&rsquo;s Annual Meeting.

While e-cigarettes may be safer than traditional cigarettes, the composition of the liquids in these devices are complex and unregulated. There is a wide variety of formulas and some may contain known bladder carcinogens such as nitrosamines, formaldehyde, acrolein, metals and acetaldehyde.

The study reported that the urine samples of e-cigarette users contained some of those known carcinogens.

&ldquo;One of the biggest impetuses for this study is that we know that e-cigarettes and vaping is a useful tool for people to stop smoking, sort of a safe alternative," said senior researcher on the study, Tatum Tarin, MD, in an interview with

"There's been a 900% increase in e-cigarettes and vaping in kids, that wouldn't be smoking otherwise. What we were trying to show is that in kids who are non-smokers, this is not exactly a safe thing, or at least we don't know the full safety profile of electronic cigarettes and vaping."

Researchers collected urine samples from thirteen e-cigarette users and ten non-smoking, non e-cigarette using controls. Using liquid chromactography-mass spectrometry, they tested the samples for five molecules that are known to be bladder carcinogens and are either present in traditional cigarettes or common solvents believed to be used in some e-cigarette formulations. Those molecules are: benzanthracene, benzopyrene, 1-hydroxypyrene, o-toluidine, 2-napthylamine. The patients self-reported abstinence from traditional cigarettes for at least 6 months prior to the specimen collection.

Twelve of the thirteen samples from e-cigarette users tested positive for two of the carcinogenic compounds: o-toluidine, and 2-napthylamine. All samples from the ten control patients tested negative for the 5 molecules. The other three carcinogens were not identified in any samples.

Tarin explained that the two molecules identified have &ldquo;been studied for a very long time, mostly in environmental exposures. They&rsquo;re known to be in people who smoked tobacco and used conventional cigarettes. O-toluidine, and 2-napthylamine are known to be bladder cancer-causing agents.&rdquo;

Additionally, 9 of the 13 e-cigarette users reported being long term nonsmokers, greater than 12 months.

Tarin also pointed out that the thirteen e-cigarette users were surveyed and &ldquo;every single one thought there were no harmful, deleterious side effects in electronic cigarettes. While they probably are a safer alternative to smoking, they are not completely safe. And that&rsquo;s what we&rsquo;re trying to show here. Compared to our control group of non-smoker, non-electronic cigarette users, [e-cigarette users] had higher levels of these bladder carcinogens.&rdquo;

Researchers determined that further studies should clarify the safety profile of e-cigarettes and their contribution to the risk of bladder cancer, given the higher concentration of carcinogenic compounds in the urine of the e-cigarette users in this study. &ldquo;It will be important to try and quantify in the long-term, to see what is the actual effects on bladder cancer, or patients who have bladder cancer,&rdquo; Tarin noted. &ldquo;The issue is, there are kids that are doing this. We don&rsquo;t want to be 50 years down the road, saying, &lsquo;Oh my god, we thought this was safe, but actually there&rsquo;s a problem.&rsquo;&rdquo;

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Study Finds Link Between E-Cigarette Use and Bladder Cancer

More Stage I cancers were diagnosed after the passage of the Affordable Care Act (ACA) within 5 screenable disease types (colorectal cancer, female breast cancer, cervical cancer, lung cancer, and prostate cancer) than were diagnosed before ACA implementation, according to findings from a study presented during a presscast in advance of the 2017 ASCO Annual Meeting.

Xuesong Han, PhD, lead researcher, explained that there is extensive evidence to suggest that a lack of health insurance or poor health insurance coverage can result in cancer being diagnosed at a later stage. The implementation of the ACA brought with it Medicaid expansion and the Marketplace exchange in 2014. These measures substantially increased the number of Americans 18 to 64 years old who have insurance coverage. With more patients on health insurance, there is more access to cancer screening and physicians, leading to earlier diagnosis of cancers that can be found via screening.

For their study, titled &ldquo;Changes in Stage at Diagnosis of Screenable Cancers After the Affordable Care Act,&rdquo; the researchers used the National Cancer Database to examine nonelderly cancer patients of screening-appropriate age in the first to third quarters of 2013, and then again in the second to fourth quarters of 2014. The number of patients with each cancer differed, as did the recommended age range for screening. The researchers determined the proportion of Stage I disease at diagnosis within each time period, as well as prevalence ratios for Stage I diagnoses in 2014 compared with 2013.

The percentage of cancers diagnosed at Stage I increased by 1% across four of the cancer types, but decreased by 1% in prostate cancer. According to the adjusted prevalence ratios, the increase in Stage I diagnoses from 2013 to 2014 was statistically significant for colorectal cancer (prevalence ratio = 1.04), female breast cancer (1.02) and lung cancer (1.07), but not for cervical cancer. The increases were, according to Han, &ldquo;consistent with our hypothesis. With more people gaining insurance and access to screening services, or access to physicians &hellip; more cancers can be detected at an earlier stage.&rdquo;

The decrease in Stage I diagnoses in prostate cancer was statistically significant (prevalence ratio = 0.93). Han, Strategic Director of Health Policy & Healthcare Delivery Research at the American Cancer Society, believes this decrease &ldquo;may reflect the recent US Preventive Services Task Force (USPSTF) recommendation against the routine testing (of prostate-specific antigen as a screening measure).&rdquo;

The researchers also considered the effect of Medicaid expansion on cancer diagnosis and screening. In states that adopted Medicaid expansion to subsidize health insurance for patients with lower incomes, health insurance was more accessible to those who were financially eligible. When the results were further stratified by states with Medicaid expansion compared to those without, the statistically significant increases for early diagnosis of colorectal cancer and lung cancer were found to have occurred only in those states that participated in the Medicaid expansion. For female breast cancer, the increase was seen in both sets of states, as was the decrease for prostate cancer.

The ACA was &ldquo;significantly associated with a shift to early stage at diagnosis for colorectal, female breast and lung cancer,&rdquo; Han concluded. Additionally, shifts to early-stage diagnosis for colorectal cancer and lung cancer were mainly seen in Medicaid-expansion states, while the shift for female breast cancer occurred regardless of Medicaid expansion.

Bruce Johnson, MD, FASCO, and President-Elect of ASCO, said of this study, &ldquo;This is certainly consistent with the idea that, by doing the additional screenings, you can potentially find more Stage I patients. And the earlier the stage, the more likely a person is to be cured.&rdquo;

Johnson also commented on the future of the healthcare system, stating, &ldquo;ASCO strongly supports the relative ease of access to screening capabilities. One of the characteristics of the ACA was that most of the cancer screening was covered. Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening which can identify cancers at an earlier stage in a more curable form.&rdquo;

Han X, Lin C, Jemal A. Changes in Stage at Diagnosis of Screenable Cancers After the Affordable Care Act.

More Stage I cancers were diagnosed after the passage of the Affordable Care Act within 5 screenable disease types (colorectal cancer, female breast cancer, cervical cancer, lung cancer, and prostate cancer) than were diagnosed before ACA implementation.

Affordable Care Act Associated With Shift to Earlier-Stage Cancer Diagnosis

Many patients with breast cancer do not receive adequate counseling or treatment for sexuality issues associated with their treatment, said Leslie Schover, PhD, founder of the Will2Love website, an online resource to help guide cancer survivors in sexual wellness and parenthood. Often, Schover said, healthcare providers do not address the topic of sexual health with their patients or follow up on their issues. In an effort to address this problem, Schover discussed strategies that can be used and steps her website is taking to promote sexual health among patients during the&nbsp;2017 Miami Breast Cancer Conference.

At least 60% of women with breast cancer end up with some form of sexual AE, according to Schover, a past professor of behavioral science at The University of Texas MD Anderson Cancer Center, where she created and evaluated innovative treatment programs for cancer and sexual health. The most common AEs are loss of desire for sex, vaginal dryness, pain related to vaginal atrophy, and difficulty reaching orgasm. These problems can lead to other physical and emotional difficulties.

The AEs are most commonly caused by systemic treatments, such as chemotherapy; these are particularly problematic in premenopausal women and can be severe and persistent. It is important, therefore, to make sure medical attention is available and utilized, Schover said. &ldquo;For patients with cancer overall, fewer than 20% ever see a health professional for 1 of these problems.&rdquo; Surveys have shown that many oncologists do not bring up the topic of sexuality at all. Further, women who do ask their providers questions about sexual health often do not find the answers helpful, Schover said.

Schover said oncological care should extend toward addressing these aspects of cancer treatment. However, she said few gynecologists or mental health professionals have the proper training or interest to treat sexual health.

Embarrassment also is another impediment because it stops women from asking questions and clinicians from raising the issue. Patients may feel their questions are a waste of the clinician&rsquo;s time. Age, cultural background, and sexual orientation also keep patients from asking about problems with sexuality. Some patients do not realize that the problems they are having with sexuality are related to the treatment they received for cancer.

Because so many factors are involved, the &ldquo;best treatment should involve not just prescribing medical treatment but also doing some counseling,&rdquo; said Schover. If the patient is in a relationship, involving the partner in treatment can be beneficial, too.

At the very least, the provider should &ldquo;ask 1 general question&rdquo; about sexuality during a patient visit, Schover said. She suggested something simple, such as: &ldquo;Many patients have problems with sexuality after this treatment. I&rsquo;m wondering how you&rsquo;re doing.&rdquo; There is also the option of using sexuality checklists as a guide for patient interaction, but these can get left by the wayside, with no follow-up, which only serves to frustrate patients further. &ldquo;They&rsquo;ve indicated that they have a problem and they expect somebody to help them,&rdquo; Schover explained, &ldquo;and nobody brings it up.&rdquo;

Schover suggested that a practice or clinic have at least 1 staff member who is trained to be the local sex and fertility expert. This person should be comfortable discussing these topics and be informed about breast cancer treatment. This same resident expert should be equipped with helpful informative materials, such as booklets, websites, and videos. It is also important to know what local specialists are available: gynecologists who understand menopause symptoms and pain, fertility clinics, etc. Schover said that the plentiful resources available in an urban center would make this job much easier than it would be for those practicing oncology care in less populated areas. The internet, however, can play a significant part in easing the burden.

Schover&rsquo;s digital health company Will2Love can be used as a resource for patients who need information about managing sexual health related to cancer treatment. Will2Love was, in fact, born of Schover&rsquo;s frustration with the lack of change in the treatment for these issues. &ldquo;I wanted there to be 1 comprehensive place where men and women with cancer could go to get answers and help,&rdquo; she explained, &ldquo;and where health professionals could go also to get some extra training and knowledge.&rdquo;

Will2Love.com offers free content including a blog by Schover, moderated online forums for both patients and healthcare professionals and an extensive list of resources. This list provides patients with names of trusted advocacy groups, experts, and sexual health product providers. There are also in-depth descriptions of how infertility can be caused by cancer treatments and the many options available for fertility preservation. Patients can also learn about the emotional issues that interact with fertility.

Recently, Schover conducted tests on the Will2Love online self-health programs developed through National Cancer Institute grants. These were randomized trials with patients from MD Anderson comparing sexual health improvements in women who used the website alone or the website with in-person counseling sessions.

Both patient cohorts improved in this trial. The group that received counseling improved faster, but had a lapse in progress. The website-only group had no such regression. &ldquo;By 6 months,&rdquo; Schover said, &ldquo;they were kind of equal, and were significantly better than where they had started off.&rdquo; Additionally, Schover said, &ldquo;women in the trial spent an average of 2.5 hours using the website, which is unusually long for online interventions.&rdquo;

Will2Love self-help programs reach across different cancer sites with information on the known sexual and fertility AEs of the common forms of cancer treatment. Emotional problems are covered as well, with help on improving sexual communication, dating after cancer, and cultural and societal attitudes that surround sexuality.

The program is also personalized. Users can set and prioritize their goals. Patients are offered articles, exercises, and suggestions for medical care, as well as information on potential barriers to sexual health and strategies for overcoming them. These features help patients to navigate all the resources the program offers.

Schover said Will2Love has plans to launch telehealth video-counseling in the near futurewith trained patient advocates and expert psychologists available. &ldquo;It&rsquo;s very hard to find someone who has expertise in those areas, outside of a very few cancer centers who have sexuality clinics, or if you live in New York, Los Angeles,or San Francisco.&rdquo;

Will2Love is also working to close the treatment gap by providing training and information for healthcare professionals in addition to patients. The &ldquo;Pro Portal&rdquo; will operate with &ldquo;online skills training and a very detailed clinician&rsquo;s manual on how to use our self-help programs with men and women.&rdquo; Healthcare professionals will be able to use the program to supplement counseling or as a follow-up to initial counseling.

In the next few months, Will2Love will begin a collaborative agreement with the American Cancer Society (ACS) to determine its effectiveness. This will involve a free pilot trial of the program via a link on ACS webpages on sex or fertility. If patients are willing to fill out questionnaires, they receive a free 3-month subscription to the program with the opportunity to renew for another 3 months.

Leslie Schover, PhD, discusses ways in which providers can better address sexuality issues associated with treatment for patients with breast cancer.

Sexual-Related Issues Need to Be Better Addressed in Women With Breast Cancer, Expert Says

During a presentation at the 2017 Miami Breast Cancer Conference, Leslie R. Schover, PhD, stressed the importance of preventive sexual counseling in reducing sexual dysfunction resulting from the treatment of breast cancer patients with aromatase inhibitors (AIs); however, she says, intervention should be provided early in treatment and supported by encouragement from providers, Leslie R. Schover, PhD, said in a presentation at the 2017 Miami Breast Cancer Conference.

Schover is the founder of Will2Love, an online resource to help guide cancer survivors in sexual wellness and parenthood. She was previously a professor of behavioral science at The University of Texas MD Anderson Cancer Center, where she created and evaluated innovative treatment programs for cancer and sexual health. She has also served as a staff psychologist at the Cleveland Clinic Foundation.

The importance of AIs and their effect on sexuality is growing as more women are being prescribed this treatment. In addition, there is potential for the course of these drugs to be extended from 5 years up to 10 years, and vaginal/vulva adverse events (AEs) grow worse the longer patients stay on AIs. These sexual issues are often overlooked or underestimated. Schover said this is because many American women over the age of 50 are no longer sexually active and because study questionnaires on sexual health are inadequate.

Schover led a survey study of 139 women within the Department of Breast Medical Oncology at MD Anderson

Cancer Center with localized breast cancer.

Ninety-three percent of the women reported some level of sexual dysfunction after using AIs as adjuvant therapy after 18 to 24 months. Additionally, 75% of the women reported being distressed about the effects AIs had on their sexual health, whereas one-quarter of the women stopped all partner sex due to severe genital pain and dryness. About 70% of women attributed sexual problems to the initiation of AI therapy. The main issues, Schover explained, were vaginal dryness and dyspareunia.

That survey provided a benchmark for a follow-up investigation: a randomized pilot trial designed to evaluate the

effect of early intervention on sexual dysfunction during the first year on AIs.

The study also sought to compare efficacy of prebiotic and hyaluronic-acid, over-the-counter, estrogen-free vaginal moisturizers.

The MD Anderson study enrolled 57 postmenopausal women with early-stage breast cancer who started AIs as first-time endocrine therapy. All of the patients received a detailed handout covering the management of AEs from AIs as well as follow-up questionnaires after 6 months and 1 year on treatment. In addition, half of the study participants received a kit of products to help treat sexual dysfunction. This included the vaginal moisturizer, water-based lubricant, a vaginal dilator, and instructions on how to use everything. This active treatment group was also given access to an online information resource and coaching over the phone. Within this active treatment group, half received the prebiotic over-the-counter vaginal moisturizer and half received the hyaluronic-acid product.

Included in the instructions that all participants received was an explanation about the importance of adhering to AI treatment. &ldquo;Usually, only maybe 50% of women finish the 5 years of an aromatase inhibitor, or of tamoxifen,&rdquo; Schover explained. This nonadherence is usually a result of the side effects AEs that women experience from these drugs, including sexual dysfunction. The aim was to use these interventions on a preventative basis, to stop the sexual problems that occur when starting on an AI.

Of the findings from this study, Schover said, &ldquo;What we had trouble demonstrating, except on a couple of

measures, was that the active treatment groups were better than the usual care. They both were in far better shape in a year than the women in our benchmark survey.&rdquo; Compared with the 24% of patients who stopped having partner sex completely in the benchmark study, only 9% stopped in this study. Sexual dysfunction was also not as prevalent in this study as it was in the benchmark study. Overall, the patients&rsquo; sexual function over the study period was fairly stable. Schover expected a sharp decline, based on the earlier data.

Schover listed several limitations, including the size of the study and the likelihood of undertreatment. The recommended frequency for the vaginal moisturizer is 5 to 7 times a week. &ldquo;We told them to use it 2 to 3 times a week,&rdquo; Schover explained. &ldquo;And when we looked at how often women actually used it, it was an average of about twice a week.&rdquo;

There was also a regression between the 6-month outcomes and the 12-month outcomes. Schover attributes this to the limited 6-month supply that the researchers gave women. &ldquo;A lot of them didn&rsquo;t go out on their own and buy more,&rdquo; she said.

Not all women used the vaginal dilator and, combined with that, there is uncertainty whether these are a viable intervention, Schover said. &ldquo;There are some data suggesting that women who are sexually inactive have more vaginal atrophy, and we don&rsquo;t know what&rsquo;s the chicken and what&rsquo;s the egg.&rdquo;

The products in this study were over-the-counter moisturizers and did not contain vaginal estrogen. Schover said

that one of the most important findings from the study was that women were able to maintain a reasonably normal sex life, or they didn&rsquo;t have their sex life decline by much.

Many patients as well as oncologists are wary of using vaginal estrogen with breast cancer and AIs. The goal

of hormone therapy for patients with breast cancer is to remove as much estrogen as possible from the system. However, as Schover explained, &ldquo;the vaginal walls and lining have many tiny blood vessels. It&rsquo;s easy for any vaginal

estrogen to get into the bloodstream.&rdquo; There are many unknowns when it comes to using vaginal estrogen, though, and it&rsquo;s difficult for clinicians to conduct safety test on this issue because &ldquo;women don&rsquo;t even want to risk participating in them.&rdquo; Also, to properly monitor the amount of estrogen in the bloodstream requires expensive equipment, which is usually reserved for research purposes.

Some women may require a hormonal, vaginal treatment to overcome painful intercourse. However, Schover is a proponent of attempting other methods first. &ldquo;Let&rsquo;s use treatment algorithms and do these &lsquo;do no harm&rsquo; approaches first, with totally nonhormonal lubricants and moisturizers.&rdquo;

Based on the results, Schover considers this a promising study that deserves a follow-up. For future studies, Schover suggests eliminating the prebiotic moisturizer, as it was &ldquo;clearly less effective&rdquo; than the hyaluronic acid-based product. Additionally, she would provide stricter instructions, a longer-lasting supply of products, and initiate follow-up check-ins sooner.

&ldquo;It&rsquo;s much better to prescribe these things and give the instructions preventively, rather than wait until women have horrible problems and have stopped sex for 6 months,&rdquo; Schover said. Further, many women just never receive adequate instructions on how to use the nonhormonal options.

Schover LR, Baum GP, Fuson LA, Brewster A, Melhem-Bertrandt A. Sexual problems during the first two years of adjuvant treatment with aromatase inhibitors.

. 2014;11(12):3102-11. doi: 10.1111/jsm.12684

Advani P, Brewster AM, Baum GP, Schover, LR. A pilot randomized trial to prevent sexual dysfunction in postmenopausal breast cancer survivors starting adjuvant aromatase inhibitor therapy. Manuscript under review.

During a presentation at the 2017 Miami Breast Cancer Conference,&nbsp;Leslie R. Schover, PhD, stressed the importance of preventive sexual counseling in reducing sexual dysfunction resulting from the treatment of breast cancer patients with aromatase inhibitors.

Allie Casey | Authors

Articles

Study Finds Link Between E-Cigarette Use and Bladder Cancer

Affordable Care Act Associated With Shift to Earlier-Stage Cancer Diagnosis

Sexual-Related Issues Need to Be Better Addressed in Women With Breast Cancer, Expert Says

Expert Stresses Importance of Pairing AI Treatment With Preventive Sexual Counseling