PFS Rises in Ovarian Cancer with Repeat Bevacizumab

ASCO 2018Women with advanced ovarian cancer previously treated with bevacizumab (Avastin) had a 3-month improvement in progression-free survival (PFS) when they received second-line therapy that included bevacizumab, European investigators reported.

Median PFS increased from 8.8 months with platinum-based chemotherapy to 11.8 months with chemotherapy plus bevacizumab, although overall survival did not improve significantly with the addition of the angiogenesis inhibitor, Sandro Pignata, MD, of the Instituto Nazionale Tumori “Fondazione G. Pascale”-IRCSS in Naples, Italy, said here at the American Society of Clinical Oncology meeting.

“In ovarian cancer patients relapsing 6 months or more after last platinum-based chemotherapy, previously treated with bevacizumab in first line, rechallenge with bevacizumab in combination with a platinum-based doublet is associated with a significantly prolonged progression-free survival with no unexpected toxicity,” said Pignata. “Rechallenge with platinum-based chemotherapy and bevacizumab is a clinical option in recurrent patients already treated with bevacizumab.”

Beyond the PFS benefit, the trial provided important insights into the biology of cancer and the role of angiogenesis inhibitors, said invited discussant Charlie Gourley, PhD, of the University of Edinburgh in Scotland. By directly targeting the cancer cell, chemotherapy triggers resistance mechanisms that are “hard-wired into the cell.” Consequently, reexposure to the same agent at disease progression “probably isn’t a good idea.”

In contrast, angiogenesis inhibitors take away the “goodies” in the tumor microenvironment. When the treatment is stopped, the “goodies” return.

“That may not be a good thing to do,” said Gourley. “Maybe we need to think about resistance to antiangiogenic therapies differently.”

In support of the comments, he noted that the hazard ratio associated with the 3-month improvement in PFS reported by Pignata (0.51) is consistent with hazard ratios of prior trials of second-line bevacizumab involving patients who had not received the angiogenesis inhibitor as part of first-line therapy. In the current study, prior exposure to bevacizumab did not appear to blunt the drug’s effect in second line.

“This was a well-powered, well-conducted study with an inclusive design,” Gourley said in conclusion. “These are potentially practice-changing results. This study improves our understanding of what we are trying to achieve with antiangiogenic therapy.”

Though not addressed in the study design, the cost associated with extended use of bevacizumab will be an issue, Gourley added.

When added to first-line platinum-based chemotherapy, concurrent bevacizumab plus maintenance improves PFS in advanced ovarian cancer. The angiogenesis inhibitor also provides benefit for patients with recurrent disease (platinum-sensitive or platinum-ineligible) and no prior exposure to bevacizumab, said Pignata, noting that 70%-80% of patients with recurrent disease are eligible for rechallenge with platinum-based therapy.

No previous trial had specifically evaluated the efficacy of adding bevacizumab to chemotherapy for patients with disease recurrence after first-line treatment that included bevacizumab.

Investigators at centers affiliated with cooperative research groups in Italy, France, Switzerland, and Greece enrolled patients with recurrent, platinum-sensitive ovarian cancer treated with bevacizumab in the first-line setting. They were randomized to receive platinum-based chemotherapy only or with bevacizumab.

The trial had a primary endpoint of PFS, and secondary endpoints included overall survival, safety, and objective response rate. The study population comprised 405 patients who had a median age of 61. About 80% of the patients had serous cancers, and 10% had BRCA mutations, although mutation assessment had yet to be performed for more than half the patients.

Two-thirds of the patients had a platinum-free interval >12 months. The most commonly used chemotherapy regimens were carboplatin-gemcitabine (48.6%) and carboplatin-pegylated liposomal doxorubicin (41.0%). A little more than half the patients had surgical debulking to <1 cm residual disease.

Three 3-month difference in PFS met prespecified criteria for statistical significance (HR 0.51, 95% CI 0.41-0.65, P<0.001). Subgroup analysis showed a consistent benefit for the addition of bevacizumab to chemotherapy. Median overall survival was 27.1 months with chemotherapy alone and 26.6 months with the addition of bevacizumab. The response rate also was similar (65.7% with chemotherapy, 74.6% with bevacizumab).

The most common grade ≥3 toxicities with bevacizumab were neutropenia (39.8%), thrombocytopenia (30.3%, P=0.04 versus the control arm), hypertension (28.9%, P<0.001), and anemia (10.9%). Proteinuria also occurred more often in the bevacizumab arm (3.9% vs 0, P=0.007).

An extensive biomarker analysis is ongoing, said Pignata.

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Pembrolizumab Monotherapy Shows Activity in Advanced Recurrent Ovarian Cancer

ASCO 2018Pembrolizumab monotherapy is associated with antitumor activity in patients with advanced recurrent ovarian cancer, interim results from the phase 2 KEYNOTE-100 study suggest.

Notably, objective response rates among study subjects increased in tandem with increased programmed death-ligand 1 (PD-L1) expression, which helps define the population most likely to benefit from single agent pembrolizumab (Keytruda), Ursula A. Matulonis reported during an oral abstract session at the annual meeting of the American Society of Clinical Oncology.

Further, no new safety signals were identified, said Dr. Matulonis, medical director and program leader of the Medical Gynecologic Oncology Program at of Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.

All patients received intravenous pembrolizumab at 200 mg every 3 weeks for 2 years or until progression, death, unacceptable toxicity, or consent withdrawal, and tumor imaging was performed every 9 weeks for a year, then every 12 weeks thereafter until progressive disease, death, or study completion.

The overall response rate (ORR) among 285 patients in Cohort A, who had one to three prior chemotherapy lines for recurrent advanced ovarian cancer and a platinum-free or treatment-free interval of 3-12 months, was 7.4%, with mean duration of response of 8.2 months. The ORR among 91 patients in Cohort B, who had four to six prior chemotherapy lines and a platinum-free or treatment-free interval of at least 3 months, was 9.9%; the mean duration of response was not reached in Cohort B.

Among all-comers, the ORR was 8.0%, including 7 complete responses and 23 partial responses. Mean duration of response was 8.2 months, and 65.5% of responses lasted at least 6 months. Further, responses were observed across all subgroups, Dr. Matulonis said, noting that responses were seen regardless of age, prior lines of treatment, progression-free/treatment-free interval duration, platinum sensitivity, and histology.

“The one factor that did predict response was a [combined positive score] of 10 or higher, where there were more responses,” she said.

The ORRs among those with PD-L1 expression as measured using the combined positive score (CPS), which is defined as the number of PD-L1–positive cells out of the total number of tumor cells x 100, was 5.0% in those with CPS less than 1, 10.2% in those with CPS of 1 or greater, and 17.1% in those with CPS of 10 or greater (vs. the 8.0% ORR in the study), she explained, noting that all complete responses occurred in those with CPS of 10 or higher.

Grade 3-4 treatment-related adverse events occurred in 19.7% of patients, and included fatigue in 2.7%, and anemia, colitis, increased amylase, increased blood alkaline phosphatase, ascites, and diarrhea in 0.8-1.3%. One treatment-related death occurred in a patient with Stevens-Johnson syndrome, and another occurred in a patient with hypoaldosteronism. Immune-mediated adverse events and infusion reactions were most commonly hyperthyroidism and hypothyroidism, and most cases were grade 1-2, she said.

KEYNOTE-100 is an ongoing study that followed KEYNOTE-028, which demonstrated the clinical activity of pembrolizumab in patients with advanced ovarian cancer. To date, KEYNOTE-100 has enrolled 376 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer and confirmed recurrence after frontline platinum-based therapy. All had a tumor sample available for biomarker analysis.

The patients had a mean age of 61 years, 64% and 35% had performance status scores of 0 and 1, respectively, and 75% had high-grade serous disease.

Median follow-up in Cohort A at the time of the current analysis was 16.7 months, and in Cohort B, the median follow-up was 17.3 months. Treatment was ongoing in 15 and 6 patients in the cohorts, respectively. Reasons for discontinuation included radiographic progression (204 and 62 patients), clinical progression (24 and 17 patients), adverse events (22 and 3 patients), and patient withdrawal (9 and 3 patients). Complete responses occurred in 1 and 0 patients in the groups, respectively.

Median progression-free survival in both cohorts was 2.1 months, and overall survival was not reached in Cohort A, while it was 17.6 months in the more heavily pretreated Cohort B.

“Recurrent ovarian cancer is the leading cause of death from gynecologic cancer. The majority of our patients relapse after first-line platinum and taxane-based chemotherapy, and the degree of platinum sensitivity will predict the tumor response rates with platinum, as well as survival time,” she said, noting that subsequent recurrences become increasingly platinum and treatment resistant.

Current treatment options in these patients include chemotherapy with or without bevacizumab; the ORRs with single-agent immune checkpoint blockade are about 10%, but in KEYNOTE-028, patients with PD-L1–positive advanced recurrent ovarian cancer had an ORR of 11.5% with pembrolizumab treatment, she said.

“With 16.9 months median follow-up, the results confirm that pembrolizumab monotherapy in recurrent ovarian cancer elicits modest antitumor efficacy,” Dr. Matulonis concluded, noting that further analysis for biomarkers predictive of pembrolizumab response are ongoing.

Invited discussant Janos Laszlo Tanyi, MD, of the University of Pennsylvania, Philadelphia, said the findings underscore the overall modest ORRs of 5.9%-15% seen with anti-PD-1 or PD-L1 monotherapy in patients with advanced recurrent ovarian cancer, but noted the importance of the finding that the subpopulation of patients with increased PD-L1 expression may experience greater benefit.

Dr. Matulonis reported consulting or advisory roles with 2X Oncology, Clovis Oncology, Fujifilm, Geneos Therapeutics, Lilly, Merck, and Myriad Genetics, and research funding from Merck and Novartis. Dr .Tanyi reported having no disclosures.

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Non-Chemo Combo Active in Ovarian Cancer

Non-Chemo Combo Active in Ovarian CancerThe combination of two targeted agents – the PARP inhibitor niraparib (Zejula) plus the checkpoint inhibitor pembrolizumab (Keytruda) — appears to elicit a durable response among women with heavily pretreated, refractory ovarian cancer, researchers reported here.

About 25% of women with platinum-resistant/refractory ovarian cancer achieved an objective response to treatment with the two drugs, and about 67% achieved disease control despite having been previously treated with up to five lines of chemotherapy and other agents, reported Panaglotis Konstantinopoulos, MD, director of translational research at Dana-Farber Cancer Institute/Harvard Medical School in Boston.

“Treatment for patients with platinum-resistant ovarian cancer remains an unmet need in medicine,” he said. “These patients have very few options.”

In his oral presentation at the American Society of Clinical Oncology annual meeting, Konstantinopoulos said the median duration of response in this group of 47 women was 9.3 months, and included women with BRCA wild-type and homologous recombination deficiency (HRD) negative tumors.

The results showed, he said, that treatment with the dual targeted agents was “remarkably consistent” in tumors across the spectrum of resistant/refractory ovarian tumors:

  • In women whose tumors exhibited BRCA mutations, 25% had an objective response and 63% had disease control
  • Among women with an HRD-positive tumor, 25% had an objective response and 69% had disease control
  • Among women with BRCA wild-type tumors, 24% had an objective response and 65% had disease control
  • Among women with an HRD-negative tumor, 27% had an objective response and 58% had disease control
  • Overall, three women had complete responses, and three had partial responses

Konstantinopoulos noted that treatment with PARP inhibitors as monotherapy has shown some activity against platinum-resistant patients with tumors harboring BRCA mutations, but little activity outside that setting. He explained that checkpoint inhibitors by themselves have shown just modest activity against ovarian cancer, but combining the treatment in preclinical models appeared to show some synergy, which is what prompted the current study.

“We thought the treatment with the two agents would provide a better response than either agent as monotherapy,” Konstantinopoulos said.

In the phase I/II TOPACIO/Keynote-162 trial, women were eligible if they were considered to be platinum-resistant by investigator assessment, although patients who had platinum-sensitive tumors who were ineligible for further platinum therapy were permitted in the study. The patients had to have undergone no more than five lines of therapy; the median number was two. About 63% of the patients had previously been on bevacizumab (Avastin) therapy.

About 21% of the patients were ineligible for further platinum therapy, 50% of the women were resistant to platinum-based chemotherapy, and 29% were judged to be refractory to platinum-based therapy.

The median age of the women was 60; a total of 71% were in Eastern Cooperative Oncology Group performance status 0, and the rest were in performance status 1. About 77% of the women had wild-type BRCA, and 57% were positive for PD-L1 expression.

All the patients had previously had platinum-based chemotherapy: 90% had been on paclitaxel, 65% had received anthracyclines, 47% had received gemcitabine; 5% had been treated with cyclophosphamide; and 3% have been treated with topotecan.

No new safety signals emerged from the dual therapy, Konstantinopoulos reported, and hematologic adverse events were minimized with the 200 mg starting dose of niraparib. Pembrolizumab 200 mg was also administered.

The study’s discussant, Charles Drake, MD, PhD, of Columbia University in New York City, suggested that the results seen in TOPACIO/Keynote-162 might have been more additive than synergistic, since historically, pembrolizumab had about an 11% objective response rate among these patients, and PARP inhibitors typically result in a 5-10% response depending on the mutation status of BRCA.

“The addition of immunotherapy with pembrolizumab may have extended the rate of activity of the PARP inhibitor niraparib,” Drake said, noting that the study reminded him of the title of the “Curb Your Enthusiasm” TV show. “The question now,” he said, “is what do we need to carry this to a larger setting?”

The answer, he suggested, is either a randomized phase II trial or clear biological evidence that the drug is working, perhaps through further laboratory work.

To read this entire article by Medpage Today, please click here.

Report: Ovarian Cancer Rates Continue to Decrease

Report: Ovarian Cancer Rates Continue to DecreaseA new report from the American Cancer Society finds rates of ovarian cancer have declined by 29% between 1985 and 2014. Ovarian cancer deaths have declined 33% between 1976 and 2015. The report, Ovarian Cancer Statistics, 2018, was published in CA: A Cancer Journal for Clinicians and as an accompaniment to Cancer Facts & Figures 2018.

Ovarian cancer is the 5th leading cause of cancer death among women in the US. Currently, there is no recommended screening test for ovarian cancer, although large scale randomized clinical studies are ongoing to identify ways to discover effective screening methods.

Some women report symptoms in the months prior to diagnosis, but often the symptoms are non-specific, and usually women who have these same symptoms do not have cancer. Still, women who have any of these symptoms, especially if they happen every day for more than a few weeks, should see their health care provider. The symptoms include bloating, pelvic, abdominal, or back pain, trouble eating as much as you’re used to, and having to urinate more often.

Ovarian cancer survival is relatively low because most cases are advanced by the time they are diagnosis due to a lack of obvious symptoms during early stages of disease. Among women diagnosed with ovarian cancer during 2007 to 2013, 47% lived at least 5 years after diagnosis.

Highlights from the report:

  • Ovarian cancer incidence rates have been decreasing since the mid-1980s. Overall ovarian cancer incidence declined by 29% from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000).
  • The death rate declined by 33% between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000). This progress is due to reductions in incidence and improvements in treatment.
  • In contrast to overall trends, which are driven by older ages, incidence of ovarian cancer among women under 65 has generally declined since at least 1975, probably reflecting uptake of oral contraceptives, which are known to reduce risk of ovarian cancer.
  • Among women who use oral contraceptives for 5 to 9 years total, risk is reduced by about 35%.
  • In addition to oral contraceptives, risk is reduced with childbirth and tubal ligation, while menopausal hormone use increases risk.
  • Incidence rates for epithelial ovarian cancer, the most common subtype, are highest in non-Hispanic whites (10.0 per 100,000) and lowest in non-Hispanic blacks (6.9 per 100,000).
  • The strongest risk factor for ovarian cancer is a family history of breast or ovarian cancer: risk is increased by 50% if a woman has a first-degree relative (mother, sister, or daughter) with ovarian cancer and by 10% if she has a first-degree relative with breast cancer.
  • Mutations in BRCA1 and BRCA2 genes account for almost 40% of ovarian cancer cases in women with a family history of the disease.
  • Genetic testing is recommended for all women diagnosed with ovarian cancer to help them and their family members make well-informed health-related decisions. A health care provider can help set up a meeting with a genetic counselor to discuss details about testing.

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Severe Folate Deficiency Associated With Olaparib for Relapsed Ovarian Cancer

Severe Folate Deficiency Associated With Olaparib for Relapsed Ovarian CancerPatients receiving olaparib (Lynparza) for relapsed ovarian cancer (OC) may develop folate deficiency, according to findings of a small case series from researchers at Rush University Medical Center in Chicago.

The researchers discovered severe folate deficiency in a patient receiving olaparib, a poly (ADP-ribase) polymerase (PARP)-inhibitor, for relapsed ovarian cancer with no plausible explanation for the adverse effect. To their knowledge, this is the first case indicating an association between olaparib therapy and folate deficiency.

Severe folate deficiency can contribute to anemia, necessitating blood transfusion, dose reduction, and/or drug discontinuation. Therefore, the researchers conducted a chart review of patients with relapsed OC undergoing olaparib therapy to determine the incidence of folate deficiency in this patient population.

The chart review identified 7 patients who were receiving olaparib therapy for relapsed OC. Six of the 7 patients had moderate to severe folate deficiency while taking olaparib. Of those 6 patients, 5 had undetectable or near-undetectable folate levels (1.6 ng/mL or lower), and 3 developed transfusion-dependent anemia within a mean 39 days after olaparib initiation and required dose reduction or drug discontinuation.

Patients who developed folate deficiency were treated with folic acid supplementation 1 mg daily. Serum folate level, anemia, and tolerability of olaparib subsequently improved.

Among the cases in this review, patients with relapsed OC treated with olaparib became folate deficient within weeks of initiating treatment. “We think that identifying and treating folate deficiency in this population is warranted, and may improve dose delivery and safety of olaparib therapy,” the researchers concluded. “Further studies should provide insight into potential interaction between PARP-inhibition, the folate pathway, and BRCA mutations in ovarian and other cancers. We are conducting translational research to elucidate the mechanism of this association.”


Shammo JM, Usha L, Richardson KJ, et al. Olaparib-induced severe folate deficiency in women with relapsed ovarian cancer: first report and case seriesJ Clin Oncol.2018;36(suppl):e17540.

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Quality Of Life Is The Name Of The Game

By: Annette McElhiney

Quality Of Life Is The Name Of The GameI will never forget in 2008 when my doctor told me, “you have ovarian cancer.” Few words in the English language provoke a stronger reaction of fear and dread than the word cancer. However, there are others like “terminal,” “palliative care,” and “hospice” that are often feared as well. First of all, every life is “terminal.” Life ends for all of us, but no one really knows when.

I was told I had a “terminal” disease with a 25%-35% chance of living 5 years and here I am 10 years later! So much for the definition of “terminal.” But, the terms I really want to discuss in this piece are “palliative care” and “hospice” because I want to dispel the fear some patients have when they are offered this type of care. answers the question, “What is palliative care?” They write, “Palliative care is care given to improve the quality of life of patients who have a serious or life-threatening disease, such as cancer. Palliative care is an approach to care that addresses the person as a whole, not just their disease. The goal is to prevent or treat, as early as possible, the symptoms and side effects of the disease and its treatment, in addition to any related psychological, social, and spiritual problems. Palliative care is also called comfort care, supportive care, and symptom management. Patients may receive palliative care in the hospital, an outpatient clinic, a long-term care facility, or at home under the direction of a physician.”

Palliative care is not a last ditch form of treatment given to dying patients, but rather a humane method of treatment designed to address the specific needs of a patient with a serious disease. Having had surgery and 18-months of chemotherapy for ovarian cancer, which left me constantly fatigued, I would have welcomed having many of my physical and emotional needs met by a team of experts; however, “palliative care” wasn’t often offered 10 years ago.  But if I were newly diagnosed with cancer and offered “palliative care” today I’d take it in a “heart beat.” My motto is: “Take all the help you can get as you will probably recover faster as a result.”

The last, and perhaps most panic provoking, term I want to talk about is “Hospice.”   Often if someone suggests to a patient that he/she “check out hospice care” the patient panics and thinks he/she is being dismissed.  That is so far from the truth!  The suggestion simply means a patient should take advantage of another level of treatment that is tailored specifically to the patient and will improve his/her quality of life.

Note how Wikipedia defines hospice, “Hospice care is a type of care and philosophy of care that focuses on the palliation of a chronically ill, terminally ill or seriously ill patient’s pain and symptoms, and attending to their emotional and spiritual needs. In Western society, the concept of hospice has been evolving in Europe since the 11th century. Then, and for centuries thereafter in Roman Catholic tradition, hospices were places of hospitality for the sick, wounded, or dying, as well as those for travelers and pilgrims. The modern concept of hospice includes palliative care for the incurably ill given in such institutions as hospitals or nursing homes, but also care provided to those who would rather spend their last months and days of life in their own homes. The first modern hospice care was created by Cicely Saundersin 1967.”

Again, note that the major thrust is on meeting the physical, nutritional, emotional, and spiritual needs of a seriously ill person. My mother had congestive heart failure and was on hospice for several years. She spent time on hospice in 3 locations: in her home, in a hospital and in a residential nursing home.  She seemed to feel supported and cared for during her many episodes.

Some patients panic when they hear the word “hospice” because in order to be eligible for “hospice” and have it paid for by Medicare or insurance companies, several doctors must state that a patient has a serious and “terminal” illness. But remember the definition of “terminal” is relative; with my bleak prognosis, I was deemed “terminally” ill and yet I am still alive and kicking today.

“Hospice” most helps those individuals who because of reactions to chemo or meds need additional help in order to achieve a good quality of life.  To illustrate the difference between the fear of hospice and the reality, a McClatcy report says, Thousands of patients who check into hospices expecting to die are winning reprieves instead. Sometimes attention from loved ones and quality care from hospice staff turn things around. Or doctors guess wrong when they predict that death is near. And sometimes long-odds medical miracles happen.”

Whatever the reason, roughly 100,000 U.S. hospice patients will win new leases on life this year. That number, which is based on Centers for Disease Control and Prevention figures, is expected to increase as baby boomers age. It’s a trend that poses exotic challenges—some wrenching, some magnificent—for hospices and for hospice patients and their families.

As a result some patients actually get better. As McClatchty writes, “Given the focused attention of hospice doctors, nurses, social workers and spiritual counselors, the patients get their minimum meds adjusted and take them regularly. They get painkillers adequate to assure a night’s sleep. They eat regularly, and their loved ones get some help and relief.”

My point is when you have a serious illness, particularly ovarian cancer, your situation may be totally different than the same disease in others for a variety of reason. Consequently, as a patient, it is in in your best interest to take advantage of all levels and varieties of care available. The name of the game truly is QUALITY OF LIFE — get it however you can!

Ovarian, Testicular Cancers May Have Familial Association

Ovarian, Testicular Cancers May Have Familial AssociationMen with testicular cancer appeared more likely than those with other malignancies to have a mother with ovarian cancer, according to study results.

Researchers at Roswell Park Comprehensive Cancer Center investigated 31 families with a history of ovarian and testicular cancer from the Familial Ovarian Cancer Registry. The registry includes data for 2,636 families.

Investigators observed a statistically significant association between men with testicular cancer and mothers with ovarian cancer (OR=3.32; P=0.004).

In addition, sisters of men with testicular cancer appeared more likely to have ovarian cancer. Although no men with testicular cancer had a paternal grandmother with ovarian cancer, one-quarter of them had a maternal grandmother with ovarian cancer.

HemOnc Today spoke with John Lewis Etter, MPH, research associate at Roswell Park and MD/PhD student at University at Buffalo, and Kirsten Moysich, PhD, MS,distinguished professor of oncology in the department of cancer prevention and control and professor in the department of immunology at Roswell Park, about the findings and their potential implications.

Question: What prompted you to investigate th e association between testicular and ovarian cancers?

Moysich: Our group previously reported evidence for an X-linked ovarian cancer susceptibility gene variant that can be passed from father to daughter, and 12.5% of women with ovarian cancer in the Familial Ovarian Cancer Registry were carriers of this allele. Because of this, we were interested in investigating for an increased rate of cancers — specifically testicular cancers — among men in families from the registry.

Q: Can you elaborate on the sibling association between testicular and ovarian cancers, and what you think that association means?

Moysich: The observed sibling association provides further evidence for an association between familial ovarian and testicular cancers. At this time, further studies must be conducted to fully interpret what this association means.

Q: How about the fact that the association seemed to run through the maternal grandmother rather than the paternal grandmother?

Moysich: The observation that more maternal grandmothers of men with testicular cancer in the registry had ovarian cancer than paternal grandmothers is consistent with the hypothesis that the association between ovarian and testicular cancers is X-linked. A father cannot pass his X chromosome to his son; thus, a grandson can never inherit his paternal grandmother’s X-chromosome. If the association is indeed X-linked, we would expect to observe less ovarian cancer among paternal grandmothers of men with testicular cancer.

Q: What is the potential impact of these findings on clinical practice?

Etter: The results from this study provide preliminary evidence for an association between familial ovarian and testicular cancers. If these results are corroborated in future studies, they may help shape new guidelines for counseling male family members in families with multiple cases of ovarian cancer. Genetic studies also may offer insight into the etiology of these diseases, as well as targets for potential screening and therapies. Also, if substantiated, our results may translate into more aggressive screening for testicular cancer among young men with a strong family history of ovarian cancer.

Q: Where will the research go next?

Etter: We have begun targeted enrollment of families with cases of both ovarian and testicular cancer into the Familial Ovarian Cancer Registry. We will conduct further studies to better understand the genetic basis of the observed association with the goal of identifying a gene target for screening and therapy. Also, what is important about this work is that we are the first to uncover this link because we oversee this unique registry that collects detailed cancer history information that is not captured in any traditional cancer population science study. – by Rob Volansky


Etter JL, et al. Cancer Epidemiol. 2018;doi:10.1016/j.canep.2018.02.005.

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