Abstract
Results of a long-term study suggest that even short durations of postmenopausal hormone therapy could increase the risk for breast cancer
Menopausal women treated with hormone-replacement therapy have a higher risk of developing breast cancer, even if they only took hormones for less than 2 years, according to a recent study carried out by French researchers. The results, published recently in the Journal of Clinical Oncology, suggest that the specific hormone combination, as well as timing and duration of treatment, all impact upon breast cancer risk.
The findings lend further support to a growing number of studies suggesting risks related to hormone therapy. Along with breast cancer, there is some evidence for an increased incidence of blood clotting and heart disease.
“…work by Clavel-Chapelon also found that if used for a period of more than 5 years, all types of hormone therapy increased breast cancer risk.”
Previously, guidelines have recommended that short-term use of hormone treatment is the safest option to relieve menopausal symptoms.
Yet the recent study, led by Dr Françoise Clavel-Chapelon from the Institut National de la Santé et de la Recherche Médicale at the Université Paris-Sud, Paris, France, found that even when only used for less than 2 years, hormone therapy initiated within 3 years of menopausal onset increased the risk of developing breast cancer by as much as 54%. The study looked at 1726 women with breast cancer out of a total of 53,310 postmenopausal women. The women were all followed for approximately 8 years during the period between 1992 and 2005. Almost 60% of the hormone therapy users studied had begun taking hormones less than 1 year after menopause onset.
Leslie Bernstein, director of the division of cancer etiology at the City of Hope National Medical Center in Duarte, CA, USA, who wrote the accompanying editorial, describes the 50% rise in breast cancer risk found by the study as ‘alarming’. The study found that, if initiated more than 3 years after the start of the menopause, short-term hormone treatment did not elevate breast cancer risk.
Short-term use of one particular type of hormone treatment – estrogen–progesterone based treatment – was not found to have any effect on breast cancer risk, regardless of when treatment began. However, further work is needed before it can be concluded that estrogen–progesterone treatment is safer.
The work by Clavel-Chapelon also found that if used for a period of more than 5 years, all types of hormone therapy increased breast cancer risk.
The authors caution that their results may not reflect the effect of hormone therapy on women worldwide, since French women often use hormone patches rather than oral formulations as preferred in other countries. Further research is needed to determine the link between breast cancer risk and orally ingested hormone treatments.
Bernstein recommends, “…using hormones briefly and only when menopausal symptoms are so intense that no other approach will work.” However, she also highlights that within 2 or 3 years after cessation of hormone therapy, the risk decreases to that of the rest of the population.
Source: Fournier A, Mesrine S, Boutron-Ruault M et al.: Estrogen–progestagen menopausal hormone therapy and breast cancer: does delay from menopause onset to treatment initiation influence risks? J. Clin. Oncol. DOI 10.1200/JC0.2008.21.6432 (2009) (Epub ahead of print).
New trials to access and compare antiretroviral-based prevention strategies in women are underway across southern Africa
A new clinical trial aims to directly determine whether the daily use of either a vaginal gel or pre-exposure prophylaxis is more effective at protecting women from HIV infection.
The Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial will enrol up to 5000 women across Uganda, South Africa, Zambia and Zimbabwe who are considered to be at risk of contracting HIV and will allow direct comparison of the prevention strategies. VOICE, a doubleblind, randomized trial, is organized by the NIH-funded Microbicide Trials Network, and is testing two antiretrovirals: tenofovir and Truvada (tenofovir + emtricitabine) against a microbicide gel that contains an active form of tenofovir.
Women were randomly placed into five study groups. Two groups will apply the tenofovir gel or a placebo gel and three groups will be given a single table form of tenofovir, Truvada or placebo. The trial is expected to last for 3.5 years. A subset of 300 women taking oral tenofovir will be monitored for possible bone density changes, and another companion study will assess factors associated with adherence.
“Women need safe and effective methods for preventing HIV that they can control themselves.”
The Phase IIb study will investigate whether the daily routine use of a microbicide improves efficacy compared with application soon before intercourse. It is hoped that this could allow women greater privacy of use and greater adherence.
“The HIV prevention field has not been without its share of disappointments. So, naturally we are excited that in VOICE we have not just one, but two promising approaches to evaluate. Hopefully, we'll find that antiretrovirals, which helped turn the tide in the treatment of HIV, can be a prevention powerhouse, too,” commented Mike Chirenje, University of Zimbabwe (Harare, Africa) and co-chair of the VOICE Study.
“Women need safe and effective methods for preventing HIV that they can control themselves. Importantly, women need methods that they are willing and able to use, because no approach can be truly effective if she leaves it in her purse or hidden in a drawer,” added Jeanne Marrazzo, University of Washington (WA, USA) co-chair with Chirenje.
All participants will receive regular HIV testing and risk-reduction counseling, and any participant who acquires an infection during the study will receive treatment and care.
Sources: National Institute of Allergy and Infectious Disease.
in brief…
Katsumata N, Yasuda M, Takahashi F et al.: Lancet DOI:10.1016/S0140–6736(09)61157–61150 (2009) (Epub ahead of print).
A new ‘dose-dense’ chemotherapy regime can improve survival in ovarian cancer patients, according to a study published in The Lancet.
Japanese researchers carried out a Phase III trial comparing two chemotherapy approaches in 637 women. Currently, a combination of paclitaxel and carboplatin is given every 3 weeks to women with advanced ovarian cancer. Katsumata and colleagues compared this method to a new dose-dependant regime, where patients were given a dose of paclitaxel every week of the trial. The dose-dependent group were found to have a 29% lower risk of cancer progression than the conventional group and a 25% lower risk of death. Michael Brookman, who wrote the accompanying Lancet commentary, explained, “The use of such dosedense therapy should be decided on an individual basis together with other options for women with advanced-stage ovarian cancer.”
Nelson H, Fu R, Griffin J, Nygren P Smith B, Humphrey L: Ann. Int. Med. 151(10) (2009).
Medications used to reduce breast cancer risk also have serious side effects. Three breast cancer risk-reducing drugs also cause side effects according to a report by the Agency for Healthcare Research and Quality, US Department of Heath & Human Services. The report is based on a study published in the Annals of Internal Medicine, which compared the effectiveness of three drugs: tamoxifen, raloxifene and tibolone. The study found that whilst all three drugs reduce the occurrence of breast cancer in women without the disease, but who have a family history of cancer or other risk factors, they each cause adverse effects.
The most common side effects of tamoxifen are flushing, vaginal discharge and itching. Raloxifene also causes flushing and other vasomotor symptoms along with leg cramps. Tibolene, which has not yet been approved for use in the USA but is commonly used in other countries, was noted to cause side effects including vaginal bleeding. The drugs were also shown to cause increased risk of blood clots, stroke and endometrial cancer. Heidi Nelson, lead author of the study, explained that, “Clinicians must ensure that women understand their individual risks for breast cancer and can favorably balance these with the unwanted effects of risk-reducing medications.”
New ovarian cancer blood test approved by US FDA
A new blood test intended to detect ovarian cancer in women with a pelvic mass that requires surgery has been approved by the US FDA.
The FDA has announced their approval of 0VA1, the first laboratory blood test that can indicate whether a known pelvic mass is malignant. The test is intended for women over 18 years of age who have already been identified for surgery based on their pelvic mass. The outcome of OVA1 should help doctors and patients decide what type of surgery should be carried out.
OVA1 was developed by California-based Vermillion Inc., CA, USA, along with Quest diagnostics and researchers at the John Hopkins University, Baltimore, MD, USA.
A blood sample is tested for five different proteins, known to mutate as a consequence of ovarian cancer. The five separate results are then combined into a numerical score of 0–10. This score tells doctors if the pelvic mass is likely to be benign or malignant.
“…the (US) FDA has announced their approval of OVA1, the first laboratory blood test that can indicate whether a known pelvic mass is malignant.”
Previous studies have shown that if a pelvic mass is malignant, patients benefit from being referred to an oncology specialist. Ovarian cancer patients have greater survival rates when surgery is carried out by a gynecological–oncologist rather than a general gynecological surgeon.
The decision to approve the test was based on a study that looked at 516 patients and compared OVA1 results with biopsy results.
In combination with other pre-surgical test results, 0VA1 helped to recognize additional patients missed by radiological tests who may benefit from referral to oncology.
The FDA stress that 0VA1 is not intended to screen for ovarian cancer. However, when carried out on patients already selected for surgery it will be useful to compliment existing tests.
The acting director of the FDA's Center for Devices and Radiological Health, Jeffrey Shuren, claims that “tests such as 0VA1 personalize and improve public health by providing patients and healthcare providers with more information to support medical decisions that impact survival rates and reduce surgical complications.”
Source: US FDA.
www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182057.htm
ACOG advises flying is safe during uncomplicated pregnancy
According to the American College of Obstetricians and Gynaecologists (ACOG), air travel is safe for pregnant women with no complications.
The recently released ACOG revised committee opinion, published in Obstentrics and Gynecology, was based on a number of studies, all of which concluded that it is safe for pregnant women to fly.
Previously it was advised that pregnant women should be informed of the increased risk of venous thrombosis associated with long-haul travel, although additional risk during pregnancy was unclear.
“Since 2001, when ACOG first issued a Committee Opinion on pregnancy and air travel, a number of observational studies have been published confirming that air travel is generally safe during an uncomplicated pregnancy,” Chair of ACOG's Committee on Obstetric Practice, William H Barth Jr, verified. The studies found that for occasional travellers, the risk of negative outcomes during pregnancy does not rise.
The main concerns surround the effects of cosmic radiation. Travellers who fly only occasionally should not be worried, as even on long haul flights they would be exposed to no more than 15% of the recommended limit of radiation. Frequent flyers, such as flight crews, may exceed this limit and are advised to consult the Federal Aviation Administration website http://jag.cami.jccbi.gov/cariprofile.asp).
“When a patient with an uncomplicated pregnancy asks about occasional flying, we should feel comfortable saying, ‘it's safe’.”
Anyone experiencing a problematic or complicated pregnancy, who is likely to require emergency medical attention, should not fly. Otherwise there are just a few basic precautions that pregnant women should follow.
It is advised that pregnant women wear seat belts throughout the whole flight in order to protect the baby should there be any unexpected air turbulence. The seatbelt is best positioned low on the hip bones.
Carbonated drinks should also be avoided on and before the flight. This is because gas expands in the stomach at altitude and this could cause discomfort.
The committee opinion also advises that pregnant women should check the flight company policy. Most companies allow pregnant women to fly up to 36 weeks, but restrictions do differ and some require documents proving gestational age.
According to Dr Barth, “When a patient with an uncomplicated pregnancy asks about occasional flying, we should feel comfortable saying, ‘it's safe’.”
Source: ACOG Committee Opinion. Air travel during pregnancy. Obstetrics & Gynecology 114(4) 954 (2009).