Abstract
According to findings published in an early online publication in the Lancet, the aromatase inhibitor (AI) anastrozole may be a potential new therapy for postmenopausal early breast cancer. The study, conducted by Japanese investigators, found anastrozole to be more effective than tamoxifen in women receiving goserelin, a hormonal therapy. The researchers have compared different therapeutic combinations to assess their relative efficacies and safety profiles to ensure patients receive the most effective treatments and experience the best possible outcomes.
“The development of AIs has helped advance the treatment of patients with breast cancer. Current third-generation AIs demonstrate increased potency, greater specificity and reduced toxicity; they were approved for the treatment of postmenopausal women with advanced breast cancer who had progressed following tamoxifen treatment and also as an alternative to tamoxifen in first-line treatment,” explains Shinzaburo Noguchi, lead author of the study, in correspondence with Future Medicine.
Two hundred and four premenopausal women with estrogen receptor-positive operable breast cancer were enrolled as part of this double-blind randomized Phase III trial (STAGE). Of these, 197 subjects were randomly assigned to receive goserelin (3–6 mg/month) in addition to either anastrozole (1 mg/day), or tamoxifen (20 mg/day) for 24 weeks before surgery.
Noguchi continues, “given that previous investigations have shown anastrozole to be as effective as tamoxifen in the neoadjuvant setting for postmenopausal women (PROACT study), and results from the ABCSG-12 have shown a similar disease-free survival for tamoxifen and goserelin as well as anastrozole with goserelin, comparing these combinations was a logical new investigation, but one that had not yet been undertaken.”
The primary end point was best overall tumor response. More patients who received anastrozole (69 out of 98 patients; 70.4%) had a complete or partial response than those in the tamoxifen group (50 out of 99 patients; 50.5%) during 24 weeks of neoadjuvant treatment. “This resulted in a greater proportion (86%) of patients in the anastrozole group having breast-conserving surgery compared with the tamoxifen group (68%)” said Noguchi. Treatment will continue in the adjuvant setting for 5 years to assess long-term outcomes.
From this primary analysis, the authors conclude that the combination of anastrozole plus goserelin could represent an alternative neoadjuvant treatment option for premenopausal women with early-stage breast cancer. Noguchi believes that “by providing more and better information about treatment interventions in real life settings, comparative effectiveness research has provided an effective way to guide current cancer treatment practice and potentially hasten the discovery of the best approaches to treatment personalization.”
Although larger studies, such as the Tamoxifen and Exemestane Trial (TEXT) and the Suppression of Ovarian Function Trial (SOFT), are needed to provide further data before any change in clinical practice is likely, the authors remain optimistic, “Our results suggest that anastrozole with goserelin in the neoadjuvant setting may be beneficial for estrogen receptor-positive premenopausal patients, in terms of tumor shrinkage and breast-conserving surgery.”
– Written by Sarah Freeston
Source: Masuda N, Sagara Y, Kinoshka T et al. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised Phase III trial. Lancet doi:10.1016/S1470-2045(11)70373-4 (2012) (Epub ahead of print).
Increased gestational diabetes risk linked to intake of certain animal fats
Gestational diabetes is a type of diabetes that develops during pregnancy and results in a number of complications during gestation and can have a negative impact on newborns. New research carried out at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (MD, USA) sought to determine whether there was a link between habitual fat intake and development of gestational diabetes mellitus. Previous studies had provided conflicting evidence on the subject necessitating a new investigation. The first author Katherine Bowers, placed the study into a broader context commenting, “This is the largest study to date of the effects of a prepregnancy diet on gestational diabetes.”
The group collected data from 13,475 women who reported a single pregnancy between the years 1991 and 2000. The number of reported gestational diabetes cases were extracted and measurements of the fat source, total fat and specific fat were taken. These were then pooled by logistic regression. The findings of the study suggested that a higher intake of cholesterol and animal fat was significantly associated with gestational diabetes. The study, however, did not demonstrate any link between levels of dietary monounsaturated fat, polyunsaturated fat and trans-fats with gestational diabetes. The study concluded that altering 5% of dietary calorie intake from animal to plant fats could result in a decrease in the risk of developing gestational diabetes of up to 7%.
The senior author of the study Cuilin Zhang summarized the findings, “Our findings indicate that women who reduce the proportion of animal fat and cholesterol in their diets before pregnancy may lower their risk for gestational diabetes during pregnancy.”
Bowers summarized the future possibilities the study opened up, “Additional research may lead to increased understanding of how a mother s diet before and during pregnancy influences her metabolism during pregnancy, which may have important implications for the baby's health at birth and later in life.”
– Written by Andreas Hadjivasiliou
Source: Bowers K, Tobias DK, Yeung E, Hu FB, Zhang C. A prospective study of prepregnancy dietary fat intake and risk of gestational diabetes. Am. J. Clin, Nutr, 95(2), 446–453 (2012).
Study provides new evidence supporting use of oral contraceptives to alleviate dysmenorrhea symptoms
A study recently conducted at the Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, (Gothenburg, Sweden) has concluded that combined oral contraceptives (COCs) are an effective treatment for primary dysmenorrhea. A group including Ingela Lindh, Institute of Clinical Sciences, Gothenburg, Sweden, conducted the study concluding that both age and COCs were independently responsible for reduced severity of dysmenorrhea.
The study collected data using postal questionnaires across a randomly chosen group of 19 year olds at three different time points. A 5-year follow-up was also conducted. Lindh outlined the approach taken by the study, “By comparing women at different ages, it was possible to demonstrate the influence of COCs on the occurrence and severity of dysmenorrhea, at the same time taking into account possible changes due to increasing age. We could also use each woman as her own control.” Lindh summarized the results of the study, “We found that combined COC use reduced dysmenorrhea by 0.3 units, which means that every third woman went one step down on the verbal multidimensional scoring system, for instance from severe pain to moderate pain, and which meant that they suffered less pain, improved their working ability and there was a decrease in the need for analgesics. On the visual analog scale there was a reduction in pain of 9 mm. Our study provides evidence for the effective relief of painful periods with combined COCs, which is important information to women who suffer from painful periods.”
One of the findings of the study was that younger women reported more severe symptoms compared with older groups. Lindh commented on this association, “We are unsure why this is. It may be due to changes in the type of COC used, for example, differences in estrogen content and progestogen type, or a different appreciation of pain in the women born in later years, in that they may be more pain sensitive or are more prepared to complain about pain than women of the same age but born earlier.”
The study appears to make a number of new options available to regulatory bodies. Lindh commented that “we are aware that drug companies have discussed with the authorities the possible design of a randomized controlled trial for the evaluation of COCs in the treatment of dysmenorrhea but this has not yet been finalized or performed. However, our study has clearly indicated a beneficial influence of COCs on the prevalence and severity of dysmenorrhea and the absence of a randomized controlled trial confirming this in no way reduces the value of this information.”
– Written by Andreas Hadjivasiliou
Source: Lindh I, Ellström AA, Milsom I. The effect of combined oral contraceptives and age on dysmenorrhea: an epidemiological study. Hum. Reprod. doi:10.1093/humrep/der4l7 (2012) (Epub ahead of print).
Statin use linked to diabetes risk in postmenopausal women
A new study, published online in the Archives of Internal Medicine, has determined a correlation between the incidence of new-onset diabetes mellitus in postmenopausal women and use of statins. Conducted by researchers at the Rochester Methodist Hospital Mayo Clinic (MN, USA), the study used data from the national Women's Health Initiative to analyze the effect of statins on health.
Annie L Culver, lead author of the study, and colleagues, analyzed data gained from the ongoing follow-up of postmenopausal women recruited by the Women's Health Initiative between 1993 and 1998. The study included data up until 2005 involving 153,840 women without diabetes and with a mean age of 63.2 years. Incident diabetes mellitus status was determined annually from enrollment and the use of statins was captured at both enrollment and in year three. The results of the study indicate that statin use at baseline is associated with an increased risk of diabetes mellitus, with 10,242 new cases of diabetes reported among the women. This association remained after using Cox proportional hazard models to adjust for other potentially confounding factors, such as age, race/ethnicity and obesity, and was observed for all types of statins.
The study concludes that increased risk of diabetes mellitus in postmenopausal women may be a class effect of statins, stating, “Given the wide use of statins in the aging population, further studies among women, men, and diverse ethnicities will clarify diabetes mellitus risk and risk management to optimize therapy.” Despite this, researchers have noted that both the guidelines for statin use set by the American Diabetes Association, and those set for nondiabetic populations, should not be altered.
– Written by Jenaid Rees
Sources: Culver L, Ockene IS, Balasubramanian R et al. Statin use and risk of diabetes mellitus in postmenopausal women in the women's health initiative. Arch. Intern. Med. doi:10.1001/archin-ternmed.2011.625 (2012) (Epub ahead of print); For the media: JAMA & Archives. Archives of Internal Medicine news release: http://pubs.ama-assn.org/homepage/media/2012a/0109.dtl#2 (Accessed 2 February 2012).
In brief…
Researchers at The University of Texas Southwestern (Dallas, TX, USA) compared outcomes in 412 women with BMI <30, with outcomes in 297 women with BMI ≥30, who had ail undergone sling procedures and other pelvic surgery. All women had a minimum follow-up of 12 months. Quality of life was found to be significantly improved after surgery in both groups. The results indicated that obesity did not appear to be a risk factor for additional complications during both sling and prolapse surgery.
This large prospective cohort study sought out to assess if fat intake increases the risk of ovarian cancer. The study used information from 695 ovarian cancer cases, during an average 9 years of follow-up. It was revealed that women in the highest quartile of fat intake had a 28% increased risk of developing ovarian cancer versus the lowest quartile of fat intake. In addition, fat intake from animal sources was shown to be positively associated with ovarian cancer risk. The researchers proposed that this association may be modified by parity and oral contraceptive use.