Can Our Genes Help Predict How Women Respond to Ovarian Cancer Treatment?

Can Our Genes Help Predict How Women Respond to Ovarian Cancer Treatment?Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

The research showed that the genes we inherit can have a significant impact on how the body processes chemotherapy drugs, which may lead to different clinical outcomes for ovarian cancer patients.

Lead researcher, led by Professor Anna deFazio from the Westmead Institute for Medical Research and Westmead Hospital, said this discovery may help doctors predict which patients will respond positively to chemotherapy.

“Chemotherapy and surgery are the standard treatment for women with ovarian cancer, but each patient responds differently.

“We wanted to know why some women respond very positively to treatment, while others suffer serious side effects, and some have a poor response,” Professor deFazio explained.

“We set out to understand which genetic factors influence how a patient processes chemotherapy”

“Our research showed that a gene called ABCC2 plays a critical role in eliminating chemotherapy from the body. ABCC2 is a drug transporter, which means it pumps a variety of different substances out of cells.

“We found that variants of this gene are associated with high rates of drug elimination, which means they pump chemotherapy drugs out of the body quickly and may cause the treatment to be less effective.

“This may explain why chemotherapy is an effective treatment for some women, but not for others,” she said.

Professor deFazio said these latest research findings are an important step towards delivering better outcomes for patients.

“Now that we are beginning to understand the role of the ABCC2 gene, and other novel gene variants that were identified in this research, we can work towards developing personalised cancer treatment for patients,” Professor deFazio concluded.

Ovarian cancer is the most lethal gynaecological cancer and ranks as the sixth most common cause of cancer-related death in women in the Western world.

To read this entire article on MedicalXpress.com, please click here.

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‘No’ to Ovarian Cancer Screening: Harms Outweigh Benefits

'No' to Ovarian Cancer Screening: Harms Outweigh BenefitsWomen should not undergo screening for ovarian cancer if they do not have signs or symptoms of the disease, as it does not improve survival but may expose women unnecessarily to surgical complications. This is the final guidance from the US Preventive Services Task Force (USPSTF), published online February 13 in JAMA.

In a grade D recommendation against the use of ovarian screening, the USPSTF says that current tests do not accurately identify whether a woman does or does not have ovarian cancer.

A false positive result may lead to a woman’s undergoing surgery to remove one or both ovaries without her having the disease.

The recommendation does not apply to women who are at high risk of developing ovarian cancer, such as those carrying BRCA gene mutations.

This final statement on ovarian cancer screening confirms a draft version of the guidelines released in July 2017, as reported by Medscape Medical News. The recommendation against routine screening also echoes recommendations of previous guidelines published in 2012 and 2004, all of which found that the potential harms of ovarian cancer screening outweighed the potential benefits.

The “evidence shows that current screening methods do not prevent women from dying of ovarian cancer, and that screening can lead to unnecessary surgery in women without cancer,” USPSTF member Michael J. Barry, MD, Massachusetts General Hospital, Boston, commented in a statement.

USPSTF member Michael J. Barry, MD, Massachusetts General Hospital, said in a release that the “evidence shows that current screening methods do not prevent women from dying of ovarian cancer and that screening can lead to unnecessary surgery in women without cancer.”

Coauthor Chien-Wen Tseng, MD, MPH, Hawaii Medical Service Association Endowed Chair in Health Services and Quality Research, who is also on the task force, called for research to find better screening methods to “help reduce the number of women who die from ovarian cancer.”

“Ovarian cancer is a devastating disease, and we do not have a good way to identify women with ovarian cancer early enough to treat it effectively,” she added.

Stephanie V. Blank, MD, professor of gynecologic oncology, Icahn School of Medicine at Mount Sinai, New York City, who was not involved in developing the recommendations, agreed that there is a lack of effective tests for the disease.

“In the general population, ovarian cancer is a relatively rare disease, and the specificity of our current tests is not acceptable,” she said in a statement. “False positives in ovarian cancer screening can result in unindicated surgeries.

However, in a related editorial in JAMA Internal Medicine, Steven A. Narod, MD, Women’s College Research Institute, Women’s College Hospital, Toronto, Canada, argues that “we should not give up entirely on ovarian cancer screening.”

He points to recent research showing that the majority of high-grade serous ovarian cancers originate in the fallopian tube and that striving to identify cancers in stages I and II is based on the false assumption that the cancer stage is the main predictor of survival.

Narod concludes: “Screening for ovarian cancer is not ready for prime time, but there are reasons why we should continue the quest.”

In an JAMA  editorial, Karen H. Lu, MD, Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, echoes the call for more effective screening strategies, but also urges the development of complementary prevention programs.

She writes: “Broadening the strategy to include accurate risk models and genetic testing, novel prevention options, and effective early detection may help reduce the incidence and high mortality associated with ovarian cancer.”

In an editorial in JAMA Oncology, Charles W. Drescher, MD, and Garnet L. Anderson, PhD, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, write that the incremental improvement of screening performance could result in meaningful benefits not yet seen in the trial data.

“Better risk-prediction tools could lead to more targeted screening and a higher likelihood of an overall benefit, even with current screening modalities,” they write. “Additional biomarkers, particularly those that are not dependent on tumor burden, may provide better screening performance and potentially at an earlier, more treatable stage.

“Imaging technology that can reliably detect tumors as small as a few millimeters in size and localized to the fallopian tubes would also likely contribute,” they add.

Recommendations Based on Systematic Review

To update the 2012 version of the UPSTF recommendations on ovarian cancer screening, the task force conducted a systematic review of the available evidence, searching the MEDLINE, PubMed, and Cochrane Collaborative Collaboration Registry of Controlled Trials databases for studies between 2003 and 2017.

They included four trials in the analysis. Three of the trials, which included a total of 293,038 women, examined ovarian cancer mortality; the remaining study, which involved 549 women, examined psychological outcomes.

Despite the inclusion of several screening interventions, including transvaginal ultrasound with or without cancer antigen 125 testing, no trial found that screening was associated with a significant difference in ovarian cancer mortality.

However, in two of the trials, 1% to 3% of women whose screening results led to surgery for suspected ovarian cancer were found not to have the disease. Major complications occurred in 3% to 15% of procedures.

There was little association between screening and psychological outcomes, although in one of the trials, repeated follow-up scans and tests appeared to increase the risk for psychological morbidity.

To read this entire article on Medscape, please click here.

Antibody-Drug Conjugate Offers Modest Improvement in Ovarian Cancer

Antibody-Drug Conjugate Offers Modest Improvement in Ovarian CancerAn antibody-drug conjugate known as lifastuzumab vedotin offered a numerical but not statistically significant improvement in progression-free survival (PFS) over pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer, according to a new phase II study.

“Single agents approved for platinum-resistant ovarian cancer have overall response rates from 6.5% to 20.5% and a PFS from 2 to 6 months. Thus, there is an urgent need for more effective therapies,” wrote study authors led by Joyce F. Liu, MD, MPH, of the Dana-Farber Cancer Institute in Boston.

Lifastuzumab vedotin (LIFA) is a conjugate of a humanized immunoglobulin G1 anti-NaPi2b monoclonal antibody and the antimitotic agent monomethyl auristatin E. NaPi2b is expressed in ovarian cancer, as well as other malignancies including non–small-cell lung cancer and papillary thyroid cancer; a phase I trial showed that LIFA was well tolerated with potential antitumor activity in platinum-resistant ovarian cancer patients.

The new phase II study included 95 patients randomized to either LIFA given intravenously every 3 weeks (47 patients) or to standard care with pegylated liposomal doxorubicin (PLD); 93 patients received at least one dose of the study drug. Patients were followed for a median of 6.6 months; the results were published in Annals of Oncology.

The median PFS with LIFA was 5.3 months, compared with 3.1 months for PLD, for a hazard ratio (HR) of 0.78 (95% CI, 0.46–1.31; P = .34). In patients with high expression of NaPi2b, the rates were similar, with a median PFS with LIFA of 5.3 months and 3.4 months with PLD, for an HR of 0.71 (95% CI, 0.40–1.26; P = .24).

In the full cohort, the objective response rate to the therapy was 34% with LIFA and 15% with PLD (P= .03). In the NaPi2b-high group, those rates were 36% and 14%, respectively (P = .02). The median duration of response was 5.5 months with LIFA and 3.9 months with PLD in the full cohort.

LIFA was generally well tolerated, with similar numbers of patients in each group reporting adverse events of any grade, grade 3 or higher events, serious events, adverse events leading to therapy discontinuation, and adverse events leading to death. Five LIFA patients (11%) had grade 2 or higher neuropathy, compared with two PLD patients (4%). More LIFA patients had abdominal pain (46% vs 28%), diarrhea (35% vs 19%), and neutropenia (28% vs 17%) vs PLD patients. More PLD patients, meanwhile, had constipation (24% with LIFA vs 38%), stomatitis (7% vs 30%), and palmar-plantar erythrodysesthesia syndrome (0% vs 26%).

“This study was hypothesis generating and was designed to detect only a large benefit of LIFA monotherapy,” the authors wrote, adding that the study confirms that antibody-drug conjugates can have significant clinical activity in platinum-resistant ovarian cancer. “However, this study also highlights that objective response rate alone may not translate to durable responses with [antibody-drug conjugates], and that careful target selection, evaluation of target expression thresholds, response rate, and duration of response may all be important to the future development of antibody-directed cytotoxics in ovarian cancer.”

To read this full article on CancerNetwork.com, please click here.

Immunotherapy Combos on Horizon for Ovarian Cancer

Several Ongoing Trials Exploring PARP Combinations in Ovarian CancerSeveral phase III studies are exploring immunotherapy combinations for patients with ovarian cancer, with the potential to disrupt the systemic treatment paradigm for these patients, according to Camille Gunderson, MD, who spoke at the SGO 2018 Annual Winter Meeting in Snowmass, Colorado.1

These larger studies for patients with ovarian cancer are testing combinations of immunotherapy with chemotherapy or anti-VEGF agents. These studies were preceded by small trials exploring monotherapy with immunotherapy. If findings from the smaller single-agent trials are proven and improved in larger phase III studies, these combinations could result in lasting treatment changes.

“There are a number of agents which enhance antigen presentation and T-cell activation, including conventional chemotherapy agents, radiation treatments, and newer, targeted agents such as PARP inhibitors,” said Gunderson, an assistant professor at the University of Oklahoma Health Sciences Center, Stephenson Cancer Center. “Antiangiogenic agents such as bevacizumab [Avastin] increase T-cell trafficking and infiltration into tumors. [Also], immunomodulatory agents block immunosuppression within the tumor microenvironment and enhance tumor cell death.”

Immunotherapy Combinations

As a single agent, the PD-1 inhibitor nivolumab (Opdivo) showed responses in 15% of patients with platinum-resistant ovarian cancer in findings published in 2015.2 Overall survival (OS) in this group reached 20 months. To push this efficacy further, several studies are assessing the combination of 2 immune checkpoint inhibitors.

Although 2 immune checkpoint inhibitors might seem like overkill, Gunderson said in this case “more is more.” She cited results published in The New England Journal of Medicine by Wolchock et al showing that 3-year overall survival (OS) for patients with previously untreated advanced melanoma was 58% for those who received a combination of nivolumab and ipilimumab compared with 52% for those assigned to nivolumab monotherapy and 34% for those assigned to ipilimumab monotherapy.3

NRG-GY003 (NCT02498600) is a randomized, open-label, phase II trial evaluating the safety and efficacy of nivolumab with or without the CTLA-4 inhibitor ipilimumab (Yervoy) in treating patients with persistent or recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer (n = 96).

One group of patients in the study was assigned to 3 mg/kg of nivolumab once every 2 weeks for 4 doses in the induction phase, then the same dose every 2 weeks for up to 42 weeks, until disease progression or unacceptable toxicity. The other group was assigned the same dose of nivolumab plus 1 mg/kg of ipilimumab once every 3 weeks for 4 doses, followed by nivolumab 3mg/kg every 2 weeks up to 42 doses.

That study has finished recruiting, with results eagerly anticipated. The estimated primary completion date for the study is December 2020.

“Although immune checkpoint inhibition has really changed the treatment for many solid tumors, particularly for melanoma and microsatellite unstable tumors, it looks like combining them really does provide a much stronger tumor kill than either agent alone,” she said.

Similarly, the phase II, single-arm DART trial (NCT02834013) is exploring the combination of nivolumab and ipilimumab in 31 rare cancers, such as nonepithelial tumors of the ovary, including germ cell tumor and Mullerian mixed tumor and adenosarcoma. The primary endpoint is overall response rate. Secondary endpoints include progression-free survival (PFS), clinical benefit rate, estimated immune-related ORR, and immune-related PFS by unidimensional immune-related response criteria.

DART’s expected completion date is August 2020.

Chemotherapy Plus Immunotherapy

Two phase III studies, JAVELIN 100 (NCT02718417) and JAVELIN 200 (NCT02580058), are evaluating avelumab (Bavencio) in combination with chemotherapy. In a prior study,4single-agent avelumab, a PD-L1 inhibitor, shored an objective response rate (ORR) of 9.7% for patients with heavily pretreated recurrent or refractory ovarian cancer. Median OS reached 10.8 months.

JAVELIN 100 is enrolling women with treatment-naïve histologically confirmed stage III-IV epithelial ovarian, fallopian tube cancer, or primary peritoneal cancer (N = 951). The 3-arm trial will compare single-agent avelumab in the maintenance setting following frontline chemotherapy; avelumab in combination with carboplatin/paclitaxel followed by avelumab maintenance; or, platinum-based chemotherapy alone followed by observation.

The primary endpoint is PFS, with OS as a secondary endpoint. Completion is scheduled for December 2021.

JAVELIN 200 is a phase III, multicenter, randomized, open-label study of avelumab alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory ovarian cancer. The study is fully enrolled, with 550 participants.

The estimated completion date for the primary endpoint of OS is March 2018, and Gunderson said the results are “eagerly awaited.”

Immunotherapy Plus Anti-VEGF Agents

The VEGF molecule is considered immunosuppressive because it directly and indirectly inhibits T-cell function, Gunderson said. Also, VEGF stimulates immunosuppressive regulator T cells, inhibits dendritic cell function, reduces the adhesion of lymphocytes to vessel walls, and induces abnormal tumor vasculature. Therefore, inhibition of VEGF could positively impact the immune system.

Investigators are currently recruiting 1300 women into the global, phase III, multicenter, 2-arm randomized IMaGYN050 trial (NCT03038100). Those in the primary tumor-reductive surgery group will receive paclitaxel, carboplatin, and the PD-L1 inhibitor atezolizumab (Tecentriq) on day 1 of each 21-day cycle for a total of 6 cycles, and bevacizumab starting with cycle 2 for a total of 5 cycles. Patients will then receive bevacizumab with atezolizumab for a total of 22 cycles of atezolizumab and 21 cycles of bevacizumab as maintenance therapy.

Participants in the neoadjuvant therapy group will initially receive paclitaxel, carboplatin and atezolizumab for 6 cycles and bevacizumab for four 21-day cycles. Interval surgery will occur between cycles 3 and 4. After 6 cycles, participants will start maintenance therapy of bevacizumab and atezolizumab for an additional 16 cycles.

In the ATALANTE trial (NCT02891824), investigators are studying atezolizumab plus bevacizumab in women with epithelial ovarian cancer (including primary peritoneal and/or fallopian tube adenocarcinoma) who have platinum-sensitive relapse. Investigators are recruiting roughly 405 patients into this phase III, randomized, double-blinded, comparative, multicenter study assessing the efficacy of atezolizumab in combination with platinum-based chemotherapy plus bevacizumab administered concurrent to chemotherapy and in maintenance.

References

  1. Gunderson C. Selection of Novel Agents for Combination Therapy with Gynecologic Cancers. Presented at: 2018 SGO Annual Winter Meeting; February 8-10, 2018; Snowmass, CO.
  2. Hamanishi J, Mandai M, Ikeda T, et al. Safety and antitumor activity of anti–PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. doi:10.1200/JCO.2015.62.3397
  3. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377:1345-1356. doi: 10.1056/NEJMoa1709684.
  4. Disis ML, Patel M, Pant S, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: Safety and clinical activity. J Clin Oncol 34, 2016 (suppl; abstr 5533).

To read this entire article on OncLive, please click here.

Several Ongoing Trials Exploring PARP Combinations in Ovarian Cancer

Several Ongoing Trials Exploring PARP Combinations in Ovarian CancerCombination regimens with PARP inhibitors have the potential to enhance the relatively modest benefit seen with monotherapy approaches in patients with ovarian cancer, according to Camille Gunderson, MD.

At the 2018 Society of Gynecologic Oncology Annual Winter Meeting, Gunderson, assistant professor, University of Oklahoma Health Sciences Center, detailed ongoing research exploring combination regimens with PARP inhibitors and other treatment modalities.

“Targeted agents have modest activity so far, but combining them is likely to make them more active,” she said. “There are a number of agents which enhance antigen presentation and T-cell activation, including conventional chemotherapy agents, radiation treatment, and also newer targeted agents, such as PARP inhibitors.”

Gunderson detailed some of the active trials currently exploring PARP inhibitors in combination with either anti-VEGF therapy or immunotherapy, to show what the future may hold for these regimens.

PARP Plus Angiogenesis Inhibitors

Gunderson said Study 19 generated a lot of excitement for olaparib as maintenance therapy in patients with ovarian cancer.1 In the trial, patients with platinum-sensitive, recurrent high-grade serous ovarian cancer (n = 265) were randomized to olaparib capsules at 400 mg twice daily (n = 136) or placebo (n = 129). Patients had received 2 or more prior regimens of platinum-based chemotherapy and experienced complete response or partial response to their most recent regimen.

The median progression-free survival (PFS) for patients receiving maintenance olaparib was 8.4 months, compared to 4.8 months for the control group (hazard ratio [HR], 0.35; P <.0001). For those with BRCA mutations, the median PFS was 11.2 versus 4.3 months for placebo, representing an 82% reduction in the risk of progression or death (HR, 0.18; P <.0001).

Findings from Study 19, along with the phase III SOLO2 trial, led to the August 2017 approval of olaparib tablets as a maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

The positive initial data with olaparib inspired a phase II trial by Joyce F. Liu, MD, and colleagues comparing cediranib, an oral antiangiogenic inhibitor of VEGFR 1-3, and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer.2 Median PFS favored the combination, at 17.7 months versus 9.0 months (HR, 0.42; 95% CI, 95% CI 0.23-0.76; P = .005).

Those results led to the initiation of NRG-GY004 (NCT02446600), a randomized, phase III trial comparing olaparib monotherapy versus the combination of cediranib maleate and olaparib versus standard platinum-based chemotherapy for patients with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. That study has finished accrual and is scheduled for completion in 2019.

A separate randomized phase II/III trial, NRG-GY005 (NCT02502266), is evaluating cediranib and olaparib alone and in combination compared with standard chemotherapy in women with recurrent platinum-resistant or platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer. Phase II results are pending, and will determine whether the study advances to phase III.

Researchers are also examining whether the addition of a PARP inhibitor can enhance the impact of the angiogenesis inhibitor bevacizumab (Avastin). The randomized, double-blind, phase III trial PAOLA-1 (NCT02477644) trial is assessing olaparib versus placebo in patients with advanced FIGO stage IIIb/IV high grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer treated with standard first-line treatment, combining platinum-taxane chemotherapy and the VEGF inhibitor bevacizumab concurrent with chemotherapy and in maintenance.

“Both arms have bevacizumab, one arm has olaparib,” Gunderson said. “It has not completed enrollment but it will very soon, and we will be excited to hear the results.”

PARP Plus Immunotherapy

Gunderson said preclinical evidence for PARP inhibitors in combination with immune checkpoint inhibitors suggests that the 2 are synergistic, and together deliver a much stronger therapeutic benefit for women with ovarian cancer. The TOPACIO/Keynote-162 trial (NCT02657889) will explore that potential in greater depth. The phase I/II trial will evaluate the safety and efficacy of combination treatment with niraparib (Zejula) and pembrolizumab (Keytruda) in patients with advanced or metastatic triple-negative breast cancer (TNBC) or recurrent ovarian cancer.

In results from a dose-finding study published last year in Annals of Oncology, the niraparib/pembrolizumab combination showed early signs of efficacy. Out of 8 evaluable patients with ovarian cancer, 4 responded and the remainder had stable disease.3 Gunderson said the response was impressive, especially for patients who were BRCA wild-type and PD-L1 negative.

Investigators are also currently recruiting patients for a phase I/II study evaluating the combination of olaparib and the CTLA-4 inhibitor tremelimumab in women with recurrent ovarian cancer harboring a BRCA1 or BRCA2 mutation (NCT02571725).

“The phase I data was recently presented at the NRG [meeting] but is not yet in the public domain,” Gunderson said. “We will continue to see what happens with this combination.”

References

  1. Gourley C, Friedlander M, Matalonis U, et al. Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC). J Clin Oncol. 2017;35 (suppl; abstr 5533).
  2. Liu JF, Barry WT, Birrer M, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014;15(11):1207-1214. doi: 10.1016/S1470-2045(14)70391-2.
  3. Konstantinopoulos PA, Sachdev JC, Schwartzberg L, et al. Dose-finding combination study of niraparib and pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or recurrent platinum-resistant epithelial ovarian cancer (OC) (TOPACIO/KEYNOTE-162). Ann Oncol. 2017;28(suppl 5). doi: 10.1093/annonc/mdx376.009.

To read this entire article on Targeted Oncology, please click here.

Screening Beyond Those With Cancer History May Be More Effective

Screening Beyond Those With Cancer History May Be More EffectiveAs genetic testing becomes more accessible with advanced technology and decreased costs, population-based testing for breast and ovarian cancer may be more cost effective in the long run, according to study results published in Journal of the National Cancer Institute.

To identify mutation carriers at an elevated risk for breast and ovarian cancer, typically those with personal or family history are tested. While this is helpful, there is still a large amount of women who are at risk and never tested, and by the time the find out, it is too late.

“Our existing health care structure is directed predominantly toward treatment rather than illness prevention,” the researchers wrote. “Advances in genomic medicine are being used to guide novel cancer treatment strategies. However, they also offer the opportunity to deliver a new population-based predictive, preventive, personalized and participatory medicine strategy for cancer prevention.”

A previous prospective randomized trial showed that population-based testing in an Ashkenazi Jewish population was acceptable, feasible, could be undertaken in a community setting, didn’t harm psychological health or quality of life, identified more than 50 percent of additional carriers, reduced breast and ovarian cancer incidence, and was extremely cost-effective.

Therefore, researchers from Barts Cancer Institute at Queen Mary University of London and Barts Health NHS Trust hypothesized that the implementation of a program to test all women in Britain, aged 30 years and older, could result in decreased amounts of breast and ovarian cancers among thousands.

“A health-economic assessment is crucial for evaluating and comparing the efficacy of different health interventions,” the researchers wrote. “This helps allocate resources across interventions and set policy to improve population health.”

Using a decision-analytic model, the researchers compared the lifetime costs and health benefits from different strategies for genetic testing. In particular they evaluated population testing for breast and ovarian cancer genes – including BRCA1, BRCA2, RAD51C, RAD51D, BRIP1 and PALB2 – compared with testing those with clinical criteria or family history for BRCA1 or BRCA2 genes.

Population testing for multiple genes appeared to be the most cost-effective strategy, and also prevented more breast and ovarian cancers compared with current screening methods. The model showed this was the case for both the U.K and the U.S.

Ranjit Manchanda, M.D., MRCOG, Ph.D., explained these findings are supported by the recent advances in genomic medicine, which offer the opportunity to deliver a new population-based predictive, preventive and personalized medicine strategy for cancer prevention.

“This could prevent thousands more breast and ovarian cancers than any current strategy, saving many lives,” he said in a press release.

“With the costs of testing falling this approach can ensure that more women can take preventative action to reduce their risk or undertake regular screening. As knowledge and societal acceptability of this type of testing increases, it can in the future provide huge new opportunities for cancer prevention and changes in the way we deliver cancer genetic testing.”

Members of Eve Appeal, the only UK national charity raising awareness and funding research in the five gynecological cancers (ovarian, womb, cervical, vaginal and vulvar), agreed with Manchanda, saying these findings could change how populations are genetically tested and treated moving forward.

“These research findings demonstrate the potential for both saving lives and costs,” Athena Lamnisos, CEO of The Eve Appeal, said in the release. “Whole-population genetic testing is cost-effective. If women identified as high-risk act on the information that they’re given, in terms risk reducing surgery, their lifetime risk of developing these women-specific cancers can be reduced. The impact that this study could have on healthcare in the future for these cancers is promising and an exciting step forward in prevention. ”

To read this full article on CureToday.com, please click here.

No Association Seen Between Antidepressant Use and Ovarian Cancer

No Association Seen Between Antidepressant Use and Ovarian CancerA meta-analysis incorporating tens of thousands of individuals found no association between the use of antidepressants and the risk of epithelial ovarian cancer (EOC).

“The concerns raised by a number of simulated epidemiologic investigations have questioned the possible association between antidepressant use and various types of cancer, including EOC,” wrote study authors led by Yun-Long Huo, MD, of the Shengjing Hospital of China Medical University in Shenyang. Epidemiological evidence has been inconsistent, and other recent analyses have had conflicting findings as well. The new meta-analysis aimed to reconcile some of those earlier reports and determine any potential risk of EOC associated with antidepressant use.

The analysis included a total of 8 published studies, incorporating 7,878 cases of EOC and 73,913 controls. All were published between 1984 and 2017 and used a case-control design, and were conducted in North America, Europe, and Asia. The results were published in the British Journal of Clinical Pharmacology.

The pooled odds ratio (OR) for ever antidepressant use and EOC risk was 1.10 (95% CI, 0.91–1.32). The same was true specifically for selective serotonin reuptake inhibitors, with an OR of 1.04 (95% CI, 0.80–1.35), and for tricyclics, with an OR of 1.01 (95% CI, 0.79–1.30). When the studies that were most heterogeneous were sequentially excluded, the OR further approached 1.00.

Six of the studies, including 7,165 cases and 71,644 controls, allowed for risk estimates, with the longest duration of antidepressant use compared with never-use. The pooled OR for EOC in these studies was 0.89 (95% CI, 0.66–1.19), with low heterogeneity among the studies. Another analysis of the intensity of antidepressant use and EOC risk again found no significant association.

The authors noted that the analysis is limited by the case-control nature of the included studies, though no recent prospective studies have evaluated the issue. Also, they could not rule out the possibility that depression itself could influence the risk of EOC rather than the use of antidepressants. “Considering that severely depressed patients are more likely to be treated with antidepressants, they might just be a surrogate marker for the depression-related incidence of EOC,” they wrote.

It was also not possible to adjust for all potential confounders, such as nulliparity and infertility, which could be associated with both EOC and antidepressant use.

Still, they wrote that “the results of the present updated meta-analysis involving the largest sample size to date…showed no association between antidepressant use and the risk of EOC.”

To read this full article on CancerNetwork.com, please click here.