Abstract
A team of Canadian researchers have identified a possible link between placental problems in pregnancy and early cardiovascular disease in women.
The results of a recently published study suggest that women who develop placental disorders, such as pre-eclampsia, gestational high blood pressure, placental abruption or placental infarction, have double the risk of developing premature cardiovascular disease.
The study followed approximately 1 million women from Ontario (Canada) after their first pregnancy, using data from the Institute for Clinical Evaluative Sciences. Of these women, 75,000 suffered from placental disorders, known as maternal placental syndrome. The women had no documented cardiovascular disease prior to birth. After an average follow-up of 9 years, 305 of these women had developed a cardiovascular disease such as heart attack, stroke or peripheral artery disease, at an average age of just 38 years.
This is double the rate of cardiovascular events experienced by those women who did not suffer from maternal placental syndrome. The risk was further increased in those women whose placental disorder led to growth retardation or death of the fetus, or if the woman was already at risk of cardiovascular disease (e.g., through tobacco smoking).
Lead researcher Joel Ray and colleagues from the University of Toronto (Canada) suggest that rather than a causative relationship, this link might be mediated by common risk factors, such as obesity or a genetic predisposition to metabolic syndromes. Dr Ray explained that “the notion here is that there would be a common mechanism that we believe would link an event that would happen in pregnancy to an event that would happen after pregnancy, a cardiovascular event, in other words. So it's not that a woman got pre-eclampsia that makes her get heart disease or stroke, but that it's her metabolic state prior to pregnancy, during pregnancy and after pregnancy that predisposes her to both maternal placental syndrome and cardiovascular disease.”
Given this potential predisposition, the team recommend that women with placental disorders are given an evaluation for cardiovascular risk factors, including high blood pressure and abdominal obesity, approximately 6 months after giving birth. Women should also be encouraged to eat a balanced diet and exercise regularly, for example by walking for 30 min/day.
“The beauty is that although a woman can't change her genetics or her family history, she can alter her health in advance of a pregnancy and after a pregnancy that's been affected by a maternal placental syndrome,” enthused Dr Ray.
Source: Ray JG, Vermeulen MJ, Schull MJ, Redelmeier DA: Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study. Lancet 366(9499), 1797–1803 (2005).
HER2/neu vaccine shows early success
Researchers led by George E Peoples at the Walter Reed Army Medical Center, Washington (DC, USA) have published the results of a trial of a vaccine against the HER2/neu protein in high-risk, node-positive breast cancer patients.
The vaccine contains E75, an immunogenic peptide from the HER2/neu protein, mixed with granulocyte–macrophage colony-stimulating factor. A total of 24 human leukocyte antigen (HLA)-A2+ node-positive breast cancer patients were vaccinated and 29 HLA-A2− node-positive patients were followed as controls.
The vaccinated patients showed an immune response and, despite the vaccinated group having a worse prognosis, disease-free survival was 85.7% in this group at 22 months' follow-up, compared with 59.8% in the control group. The rate of recurrence was 8% in vaccinated patients versus 21% in the controls.
Peoples commented that the “reduction in recurrences in our vaccinated breast cancer patients is similar to the recent reports using Herceptin® – trastuzumab – a monoclonal antibody that targets the same HER2/neu protein as our vaccine. Preclinical data suggest that the two may be synergistic.”
Source: Peoples GE, Gurney JM, Hueman MT et al.: Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. J. Clin. Oncol. 23(30), 7536–7545 (2005).
in brief…
Romond EH, Perez EA, Bryant J et al.: N. Engl. J. Med. 353(16), 1673–1684 (2005).
Presents the combined results of the National Surgical Adjuvant Breast and Bowel Project (NSABBP) B-31 trial and the North Central Cancer Treatment Group (NCCTG) N9831 trial. The trials compared adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel weekly or 3-weekly, alone or with concurrent trastuzumab treatment, in women with surgically treated HER2-positive breast cancer. The group who received transtuzumab (52 weeks, initatiated concurrently with paclitaxel) had a significantly reduced risk of recurrence or death and a 12% increase in disease-free survival at 3 years.
Cnattingius S, Torrang A, Ekbom A, Granath F, Petersson G, Lambe M: JAMA 294(19), 2474–2480 (2005).
Examines the association between indirect markers of hormonal exposure during pregnancy (e.g., placental weight) and risk of breast cancer. A total of 314,019 Swedish women were followed after a birth until occurrence of breast cancer, death or end of follow-up. The risk of breast cancer was greater in women whose placentas weighed 500–699 g in their first pregnancy and at least 700 g in their second, compared with women whose placentas weighed under 500 g in two consecutive pregnancies. The risk was even greater in women whose placentas weighed over 700 g in two pregnancies, supporting an association between hormone levels during pregnancy and subsequent breast cancer risk.
Katchman EA, Milo G, Paul M, Christiaens T, Baerheim A, Leibovici L: Am. J. Med. 118(11), 1196–1207 (2005).
Analyzed the results of 33 trials of oral antibiotic treatment of uncomplicated cystitis in women to determine the efficacy and safety of 3-day compared with 5-day or longer (prolonged) regimens. Symptomatic cure was achieved at similar rates with both 3-day and prolonged regimens, although the 3-day treatment was less effective in achieving bacteriologic cure. The 3-day antibiotic therapy was associated with fewer side effects.
Breastfeeding lowers risk of diabetes in the mother
A study published recently in the Journal of the American Medical Association suggests that every year a woman breastfeeds reduces her risk of Type 2 diabetes by 15%.
Researchers at the Harvard Medical School, Boston (MA, USA) analyzed data from 83,585 women in the Nurses Health Study and 73,418 women in the Nurses Health Study II who had given birth. They corrected for a variety of factors, including diet, exercise and smoking status, but still found a significant reduction in the risk of diabetes of 15%/year spent breastfeeding, for at least 15 years afterwards.
“Those studies show that metabolism, lactation, and reproduction are all tied together in a potentially interesting way,” commented lead author Alison M Stuebe. Stuebe hypothesizes that “in some way, pregnancy is a prodiabetic state; you have more resistance to insulin, and that's part of the way the body makes sure that the fetus gets enough sugar. Then comes lactation which, in a sense, is an antidiabetic state.”
Stuebe feels that breastfeeding is the best option all round, conluding that this study “gives us more reasons to encourage women to breastfeed: it's good for babies and it's good for mothers.”
Source: Stuebe AM, Rich-Edwards JW, Willett WC, Manson JE, Michels KB: Duration of lactation and incidence of Type 2 diabetes. JAMA 294(20), 2601–2610 (2005).
FDA releases official warning regarding hormone levels in the contraceptive patch
The contraceptive patch, marketed by Johnson & Johnson as Ortho Evra®, results in higher than average estrogen levels than the oral contraceptive pill, leading the US Food and Drug Administration (FDA) to order a warning to be placed on packaging.
It is unclear whether the greater dose of estrogen is harmful, but high levels of estrogen in oral contraceptives and hormone replacement therapy have been found to be associated with an increased risk of blood clots.
The new warning will state that women using the patch receive 60% more estrogen than those using a typical oral contraceptive pill with 35 mg estrogen, due to a difference in the metabolism of the drugs. The agency suggests that “women taking or considering using this product should work with their health care providers to balance the potential risks related to increased estrogen exposure against the risk of pregnancy if they do not follow the daily regimen associated with typical birth control pills.”
A total of 10 million prescriptions were written for Ortho Evra last year in the USA, with its popularity particularly high among younger women. So far there is no evidence that these users are suffering any serious adverse effects; however, the drug company Ortho McNeil have launched a study to investigate the rate of blood clots in patch users compared with users of the oral contraceptive pill.
The Wall Street Journal recently reported that the warning has made doctors wary, and several university health services have either discontinued prescriptions of the patch or are considering doing so.
Source: US FDA Press release.
Available at: www.fda.gov
Postmenopausal women with heart disease should take aspirin
A recent study has confirmed the effectiveness of aspirin in preventing heart disease-related deaths in postmenopausal women with cardiovascular disease, demonstrating that even a low daily dose of aspirin can significantly reduce the risk of death in this population.
“Women with cardiovascular disease should be on aspirin” unless there is a medical reason they are unable to tolerate it, stated Jeffery Berger, lead author of the study.
In this nonrandomized study, investigators analyzed Women's Health Initiative (WHI) data on 8928 women aged 50–70 years with cardiovascular disease, for example, those who had experienced a stroke or heart attack or suffered from cardiac chest pains. Only 46% of these women were taking aspirin, despite current guidelines recommending its use. It is unclear why this is the case, but Dr Berger speculated that “although we know that aspirin is effective, there's not much data about aspirin in women, so the message may not have come across as strong as it should have. Also, because aspirin is over-the-counter, people do not look at it as a lifesaving medication.”
Regular aspirin use may reduce the risk of death from heart disease by 25% in postmenopausal women with cardiovascular disease, according to the results of a longitudinal study, announced at the annual American Heart Association meeting.
After a mean follow-up of 6.5 years, women who regularly took aspirin had a 17% reduction in death rate from any cause and a 25% reduction in the risk of dying from heart disease. This reduction in risk was the same no matter whether the dose was 81 or 325 mg, suggesting that even a low dose of aspirin is effective when taken regularly, but further, randomized, trials will be needed to confirm this.
Berger hopes that these results, although not conclusive, will encourage women with heart disease and their physicians to consider long-term aspirin treatment.
Source: Berger J, Brown DL, Burke GL et al.: American Heart Association Annual Meeting, Dallas, TX, USA (2005) (Abstract 3802).
Women with lung cancer survive longer than men
Women appear to have a survival advantage over men in early stage lung cancer, according to a study analyzing data from 18,967 cases. The information was taken from the Surveillance, Epidemiology and End Results (SEER) registry and showed that women had significantly better survival regardless of treatment type.
Lead author Juan P Wisnievsky believes that the results “should affect the design and analysis of clinical trials…which may benefit from stratification by sex, and may be incorporated into prognostic classifications.”
The investigators grouped the cases into four treatment types: radiation, surgery, chemotherapy or no treatment. Women fared better in all four groups, with an average 5-year survival rate of 53% in women compared with 40% in men.
Dr Wisnievsky commented that this “suggests that lung cancer in women has a different intrinsic biological behavior and natural history than in men.”
Source: Wisnivesky JP, Iannuzzi M, McGinn TG, Halm EA: Gender differences in survival of patients with non-small cell lung cancer: do tumors behave differently in women? Chest Meeting Abstracts 128, 170S (2005)
Treatment for Hodgkin's lymphoma often induces amenorrhea
Many women cease menstruation after chemotherapy for Hodgkin's lymphoma, according to a study published recently in the Journal of Clinical Oncology. While 90% of women with advanced Hodgkin's lymphoma had a regular menstrual cycle before treatment, chemotherapy caused amenorrhea in the majority of these patients.
The authors stress the importance of discussing the likelihood of amenorrhea and infertility with female patients. “Patients have to be informed precisely about all late toxicities that might appear,” stated study author Karolin Behringer.
Interestingly, the risk of amenorrhea appeared to be lowered in women using the oral contraceptive pill, with only 10% of oral contraceptive users developing amenorrhea, compared with 44% of nonusers. The authors recommend that this potential protective effect of the oral contraceptive pill be studied further.
Age at time of treatment, stage of disease and chemotherapy regimen were also important factors affecting the risk of amenorrhea in Hodgkin's lymphoma patients.
Source: Behringer K, Breuer K, Reineke T et al.: Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin's Lymphoma Study Group. J. Clin. Oncol. 23(30), 7555–7564 (2005).
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