Abstract
A study has suggested that IVF is linked to an elevated risk of venous thromboembolism (VTE) and pulmonary embolism (PE) in the first trimester of pregnancy.
To date, it is estimated that 5 million individuals have been born as a result of IVF; helping some of the 10% of couples who have been affected by fertility issues.
Blood clots are already a well-known risk during normal pregnancy. In IVF pregnancies, blood clots are reported more often than in normal pregnancies; however, as yet there is no clear information on one of the leading causes of maternal death – the risk of artery blockage following IVF. In the present study, researchers from the Karolinska Institute (Stockholm, Sweden) decided to determine and compare the risk of PE with VTE in 116,960 women who underwent a normal pregnancy with 23,498 women who experienced an IVF pregnancy. The women were matched on age and time period of the births that took place between 1990 and 2008. In both groups, the average age of the women was 33 years.
In women who underwent IVF, VTE was diagnosed in 4.2 in every 1000 women, in comparison with 2.5 in every 1000 women who underwent a normal pregnancy. During the first trimester the risk increased; 1.5 cases in the IVF-exposed women in comparison with 0.3 in the normal pregnancy women. However, there was no difference in risk of VTE in the year following delivery and prior to the pregnancy.
In the IVF group, 19 women with PE were identified (0.08%), in comparison with the 70 women in the control group (0.05%). In the IVF group the risk of PE remained elevated throughout the pregnancy and in particular during the first trimester. The absolute risks for PE were low; with two to three additional cases in every 10,000 women who had undergone IVF. However, the researchers point out that PE is a complicated condition to diagnose and, as it still represents a leading cause of maternal death, these results are important findings for physicians.
Researchers adjusted the following factors: family situation, country of birth, education, BMI, maternal age, smoking, the calendar year of delivery and parity.
Researchers deduced that an increased risk of blood clots exists in addition to an increased risk of artery blockage in pregnancy following IVF. The researchers recommend that all physicians should be aware of these results as this is a potentially fatal condition and women at risk should be identified.
– Written by Priti Nagda
Source: Henriksson P, Westerlund E, Wallen H, Brandt L, Hovatta O, Ekbom A. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilization: cross sectional study. BMJ 346, e8632 (2013).
Less invasive surgery does not increase risk in early-stage breast cancer patients
“For those women who have the option, it appears that those choosing lumpectomy can be confident that less surgery is at least as good or maybe even better than a more invasive procedure.”
Treating early-stage breast cancer patients with lumpectomy and radiotherapy rather than mastectomy does not negatively affect survival, according to study.
Published online in the journal Cancer, a comparative effectiveness study suggests that there is no difference in survival for women treated with breast conserving surgery and radiotherapy compared with women treated with mastectomy for early-stage breast cancer.
Using data from the California Cancer Registry, the investigators compared long-term outcome data for the two treatment types in women with stage I or II breast cancer, subdividing this by patient age and the hormone status of the tumor.
Shelley Hwang (Duke Cancer Institute, Durham, NC, USA), lead author of the study, explained the motivation behind the research: “The clinical studies that compared lumpectomy and radiation with mastectomy showed that both groups did equally well. However, those studies were conducted over 30 years ago. We were interested to know whether the results of the clinical trials were seen in the real world among women treated with more modern breast cancer treatments.” The authors also studied a large enough group of patients to allow subgroup analysis of the data.
Talking to Women's Health, Hwang explained the results of the study: “What we found was that not only did women choosing lumpectomy do as well as mastectomy, but women over 50 years with hormone-sensitive tumors were actually 14% less likely to die of breast cancer, and less likely to die of any cause.”
Hwang emphasises that the evidence is not yet fully complete: “As an observational study, we cannot state that there was a direct link between lumpectomy and survival,” although Hwang comments that: “We did find that women who were treated with lumpectomy were less likely to die of breast cancer. This may be related to lumpectomy, but could also be due to factors that we may not know about.”
Data from over 112,000 women with early-stage breast cancer were included in the analysis; more than 60,000 women with lumpectomy and radiation treatment and over 50,000 with mastectomy and no radiotherapy were studied.
The less invasive, breast-conserving treatment was shown to have improved overall and disease-specific survival when compared with mastectomy, with the greatest benefit in older women (above 50 years of age) negative for hormone receptors.
Hwang thinks that the findings of this study could change the decision-making process for some patients: “For those women who are really on the fence and struggling with this decision and feeling that lumpectomy may not be aggressive enough treatment, I feel I can really reassure them that it is.” Hwang is hopefully about future trials in this area, commenting: “We could find that lumpectomy may even be better.”
In Hwang's opinion, “Future research should be focused on why this difference between the lumpectomy and mastectomy groups exist.” She continues that further validation of the results in other large data sets would also be useful.
Hwang concludes that “For those women who have the option, it appears that those choosing lumpectomy can be confident that less surgery is at least as good or maybe even better than a more invasive procedure.” She feels that “Studies similar to this one will hopefully help women in making these complex decisions about their health.”
– Written by Alisa Crisp
Source: Hwang ES, Lichtensztajn DY, Gomez SL, Fowble B, Clarke CA. Survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status. Cancer doi:10.1002/cncr.27795 (2013) (Epub ahead of print).
Women suffering from migraine with aura may be at higher risk for heart and blood vessel problems
Women who suffer from migraines with accompanying aura – characterized as the perception of flashing lights – could be at higher risk for heart and blood vessel problems, one study has shown. Another study indicates that women using newer contraceptives and who suffer from migraines have a higher incidence of developing blood clots. Both studies are due to be presented at the American Academy of Neurology's 65th Annual Meeting to be held on 16–23 March 2013 in San Diego (CA, USA).
The first study showed an indication that migraine with aura strongly contributes to cardiovascular events such as stroke and heart attacks developing. The Women's Health Study consisted of 27,860 female participants. Of these, 1435 women had migraine with aura. This 15-year long study documented 1030 cases of stroke, heart attack or death arising from a cardiovascular cause. The study examined the contribution that a variety of vascular risk factors had towards these cardiovascular events.
The study author Tobia Kurth (Institut National de la Santé et de la Recherche Médicale [NSERM], Bordeaux, France and Brigham and Women's Hospital, Boston, MA, USA) explained that “After blood pressure, migraine with aura was the second strongest contributor to risk of heart attacks and strokes.” Kurth further explained that “it came ahead of diabetes, current smoking, obesity and family history of early heart disease.”
“After blood pressure, migraine with aura was the second strongest contributor to risk of heart attacks and strokes.”
Kurth highlighted that whilst migraine with aura leads to the possibility of a higher then usual chance of cardiovascular events, not everyone who suffers from migraines with aura will be at risk. Those that are at risk can lessen their chances by making healthy lifestyle choices such as exercising, not smoking and keeping their blood pressure low.
The second study investigated the occurrence of blood clots in women suffering from migraine and who were also on hormonal contraceptives. The study had 145,304 female enrollments. The study included women who had migraine with and without aura and who were taking newer contraceptives such as the patch and older hormonal contraceptives. In total, of the 145,304 women who were taking contraceptives, 3437 had migraine without aura and 2691 had migraine with aura. The results showed that women who had migraine with aura had an increased chance of suffering from blood clot complications. For instance, 7.6% of women who had migraine with aura and had used a newer hormonal contraceptive had deep vein thrombosis compared with the 6.3% who had migraine and no aura. However the timing of these events is not certain. Blood clot complications were more common in women who suffered migraine and also took contraceptives than in women who did not suffer migraines but took contraceptives.
The author of the study Shivang Joshi (Brigham and Women's Falkner Hospital, Boston, MA, USA) explained the importance of the results, “Women who have migraine with aura should be sure to include this information in their medical history and talk to their doctors about the possible higher risks of newer contraceptives.”
– Written by Priti Nagda
Source: American Academy of Neurology press release. Migraine with aura may lead to heart attack, blood clots for women: www.aan.com/press/index.cfm?fuseaction=release.view&release=1133
Two-step immunotherapy technique shows promise against advanced ovarian cancer
Researchers from the University of Pennsylvania (PA, USA) have demonstrated that a dual-step personalized treatment strategy can trigger an antitumor immune response in patients diagnosed with late-stage ovarian cancer.
In the study, recently published in OncoImmunology, researchers treated six advanced ovarian cancer patients whose cancers had progressed on standard therapy with the two-stage protocol. First, the team prepared an individualized dendritic cell vaccine for each patient from tissues from the patient's tumor which was stored at the point of surgery. Dendritic cells were harvested using apheresis and subsequently exposed to the tumor extract. Following this priming process, patients were vaccinated with their individualized dendritic cells and given a combination regimen of bevacizumab and cyclophosphamide.
Of the six women who received the vaccine, four developed an antitumor response, indicating the efficacy of the approach. Of these, one patient, who entered the study with no measurable disease postsurgery, has maintained remission for 42 months following vaccine treatment. The remaining three women who demonstrated an immune response postvaccination still had residual disease and continued onto the second stage of treatment.
T cells were harvested from each of these three women and grown in the laboratory before being reintroduced into each patient subsequent to her undergoing a regimen of lymphodepleting chemotherapy. This treatment step acts to amplify the antitumor response set up by the dendritic cell vaccine.
Following this second treatment stage, two of the three women demonstrated a restored immune response. Of these, one patient continued to have stable disease, whereas the other demonstrated a complete response to the therapy.
“What we proved in this study is that this is a safe treatment strategy.”
This immunotherapeutic treatment strategy was also found to be well tolerated, with author Lana Kandalaft (University of Pennsylvania, PA, USA) stating: “What we proved in this study is that this is a safe treatment strategy. It is a walk in the park for patients, especially compared with standard chemotherapies and surgical treatments for ovarian cancer – literally, some patients left the clinic and went for a walk in a nearby park after their treatment.”
These early results are promising and have led to the commencement of a larger trial in which the researchers are aiming to enroll approximately 50 women in the hope of developing an immunotherapeutic alternative to poorly tolerated intensive chemotherapy.
– Written by Hannah Wilson
Source: Kandalaft L, Powell D, Chiang C et al. Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo costimulated T cells in recurrent ovarian cancer. Oncolmmunology 2(1), 1–9 (2013).
Non-HER2 patients might still benefit from anti-HER2 therapy
Recent DNA sequence studies suggest that more patients may benefit from currently available, highly efficient HER2-targeted drugs.
The researchers, from Washington University in St Louis (MO, USA), compiled data from 1500 patients across eight breast cancer genome-sequencing studies and identified 25 patients with HER2 somatic mutations. These patients lacked the HER2 gene amplification usually required to identify HER2-positive cancers and therefore had not previously been offered anti-HER2 therapy. The study, recently published online in Cancer Discovery, estimated that HER2 somatic mutations, such as those identified in this group of patients, may be responsible for tumor growth in 1.5–2% of all breast cancer patients. Such a figure would translate into more than 4000 patients in the USA alone each year.
The phenotype of these mutations was determined through in vitro kinase assays, protein structure analysis, cell culture and xenograft experiments. It was demonstrated that over 50% (seven out of 13) of the mutations were activating and have thus been postulated to drive tumorigenesis. Two of the mutations were found to be lapatinib resistant; however, the majority of the mutations were observed to be sensitive to the irreversible kinase inhibitor neratinib, a novel anti-HER2 therapy currently in Phase II trials. First author Ron Bose (Washington University, St Louis, MO, USA) has however warned that some of these HER2 mutations are silent and will therefore not respond to any anti-HER2 treatments.
The findings of this study have led to the commencement of a Phase II clinical trial to examine the effectiveness of anti-HER2 therapies in stage IV breast cancer patients with somatic HER2 mutations who have been classified as HER2 negative. Eligible patients will be treated with neratinib in addition to standard treatment. The trial will take place at Washington University, the Dana-Farber Cancer Institute (MA, USA), Memorial Sloan-Kettering Cancer Center (NY, USA) and the University of North
Carolina, Chapel Hill (NC, USA).
This study clearly demonstrates the value of sequencing the DNA of cancer patients with Bose stating: “If we can identify mutations that we can act on, that information will help us to better guide treatment. In this case, we don't even have to develop new drugs against HER2 mutations. It is just a matter of finding these patients.”
– Written by Hannah Wilson
Sources: Bose R, Kavuri SM, Searleman AC et al. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. doi:10.1158/2159–8290.CD-12-0349 (2012) (Epub ahead of print); Washington University in St Louis press release: http://news.wustl.edu/news/Pages/24672.aspx
About the Bulletin Board
The Bulletin Board highlights some of the most important events and research in the field of women's health. If you have newsworthy information, please contact:
Charlotte Barker, Commissioning Editor, Women's Health, Future Medicine Ltd, Unitec House, London, N3 1QB, UK