The FBI is investigating how much the manufacturer knew about the safety of the design. Plus, how does the clotting profile of new oral contraceptives compare to earlier formulations and a look at the impact of the PALB2 mutation on breast cancer prognosis.
What manufacturer Johnson & Johnson (J&J) knew about the safety of its morcellators and when is the subject of an investigation by the Federal Bureau of Investigation (FBI), according to several news reports. Coverage by The Wall Street Journal and The New York Times cites interviews with several individuals who spoke to the FBI as part of the probe but both accounts indicate that the agency itself refused to comment.
The FBI, it appears from the interviews, is attempting to determine whether J&J knew more about possible hazards of power morcellation than it reported before taking its device off the market. In April 2014, the Food and Drug Administration (FDA) issued a safety communication discouraging use of power morcellation during hysterectomy or myomectomy for fibroids because of concern about risk of inadvertent spread of unsuspected cancer to abdominal and pelvic cavities. Three months later, J&J removed its morcellation device from the market. The FDA estimates that approximately 1 in 350 women undergoing hysterectomy or myomectomy for treatment of fibroids has an unsuspected uterine sarcoma.
The actions by FDA and J&J followed a nationwide campaign to ban morcellation, led by a patient with an unsuspected sarcoma who underwent the procedure and whose disease spread. She, her husband, and a pathologist who was not involved in her case have been interviewed by the FBI, according to TheNew York Times account. The Wall Street Journal said that J&J has acknowledged correspondence with the pathologist, and that “his concerns spurred the company to revise its instructions for the [morcellation] device.” The patient’s husband reportedly contacted an FBI agent because he “suspected that morcellator manufacturers and some doctors and hospitals using the devices had violated a federal law requiring that adverse events be reported to the FDA,” said The New York Times report.
Do newer COCs mean higher risk of blood clots?
The role of individual progestins in risk of venous thromboembolism (VTE) associated with combined oral contraceptives (COCs) has long been the subject of study and debate. Results of two nested case-control studies by British investigators suggest that risk of VTE may be higher for third-generation progestins than for second-generation progestins with one exception: norgestimate.
Published in The British Medical Journal, the findings are based on analysis of data from women aged 15 to 49 who were first diagnosed with VTE from 2001 to 2013. The patients were seen in general practices in the United Kingdom that contributed data to the Clinical Practice Research Datalink (CPRD, 618 practices) and the QResearch primary care database (722 practices). Each of the women with VTE were matched with up to 5 controls by age, practice, and calendar year. The odds ratios for VTE were adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs, something not done in some previous studies.
A total of 5062 cases of VTE were identified in CPRD and 5500 in QResearch. Overall, current exposure to any COC was linked with an increased risk of VTE (adjusted odds ratio [aOR] 2.97, 95% confidence interval [CI] 2.78 to 3.17) when compared with no exposure in the previous year.
Risks of VTE were significantly higher in women with exposure in the last 28 days to gestodene (aOR = 3.64, 95% CI 3.00 to 4.43), cyproterone (aOR = 4.27, 95% CI 3.57 to 5.11), desogestrel (aOR = 4.28, 95% CI 3.66 to 5.01), and drospirenone (aOR 4.12, 95% CI 3.43 to 4.96) than with current exposure to second-generation contraceptives such as levonorgestrel (aOR = 2.38, 95% CI 2.18 to 2.59), norethisterone (aOR = 2.56, 95% CI 2.15 to 3.06), and to norgestimate (aOR = 2.53, 95% CI 2.17 to 2.96). The number of extra cases of VTE per year per 10,000 treated women were highest for desogestrel (14, 95% CI 11 to 17) and cyproterone (14, 95% CI 11 to 17) and lowest for levonorgestrel (6, 95% CI 5 to 7) and norgestimate (6, 95% CI 5 to 8).
Investigators concluded that the risk of VTE with use of COCs was higher for the new drug formulations, excluding norgestimate, than for pills that included second-generation progestins. Their findings, they noted, represented more than twice the number of VTE cases reported in the largest previous study of VTE and COCs and an additional 4 years’ worth of data.
Gene mutation tied to worse breast cancer prognosis
A gene known to predispose women to breast cancer also may signal an increased risk of death from the disease, according to the results of a new Polish study. Published in The Lancet Oncology, the data-from more than 12,000 patients-shed new light on the impact of a PALB2 mutation.
For the research, 12,529 women with invasive breast cancer from 18 hospitals in Poland were genotyped for 2 mutations in PALB2: 509_510delGA and 172_175delTTGT. A control group of 4702 women also was prospectively recruited. The study’s primary endpoint was death, which was confirmed by medical records from the Polish Ministry of the Interior and Administration. The 10-year survival of PALB2 carriers was compared with non-carriers.
A PALB2 mutation was found in 116 of the 12,529 women who were genotyped (0.93%, 95% confidence interval [CI] 0.76- 1.09) and in 10 (0.21%, 0.08 – 0.34) of the 4702 controls (odds ratio 4.39, 95% CI 2.30–8.37; P<0.0001). The 10-year survival rate for women with breast cancer and a PALB2 mutation was 48.0% (95% CI 36.5 – 63.2). For women with breast cancer but no mutation, the 10-year survival rate was 74.7% (95% CI 73.5% - 75.8%), for an odds ratio for death of 2.27, 95% CI 1.64–3.15; P<0.0001.
Investigators concluded that women with PALB2 mutation face an increased risk of breast cancer and may have a higher rate of death from the disease than those who don’t have the mutation. Increased surveillance they said, should be offered to women who carry the mutation but do not have breast cancer.