Objective This study reports the gynecologic conditions in postmenopausal women (intact uterus on enrollment) in the National Surgical Adjuvant Breast and Bowel Project (NSABP) study of tamoxifen and ...raloxifene (STAR)/P-2 trial. Study Design This study, with a median follow-up period of 81 months, evaluated the incidence rates/risks of gynecologic conditions among women who were treated with tamoxifen and raloxifene. Results Compared with women who received tamoxifen therapy, women who received raloxifene therapy had a lower incidence of uterine cancer (relative risk, 0.55)/endometrial hyperplasia (relative risk, 0.19), leiomyomas (relative risk, 0.55), ovarian cysts (relative risk, 0.60), and endometrial polyps (relative risk, 0.30) and had fewer procedures performed. Women receiving tamoxifen therapy had more hot flashes ( P < .0001), vaginal discharge ( P < .0001), and vaginal bleeding ( P < .0001). Conclusion Our results suggest that tamoxifen has more of an estrogenic effect on the gynecologic reproductive organs. These effects should be considered in counseling women on options for breast cancer prevention.
Breast cancer risk factors have been studied for the past three decades, and the single most important risk factor is age. Hormonally linked adult reproductive and anthropometric risk factors ...contribute to the etiology of postmenopausal breast cancer. The risk of breast cancer increases among women older than 50 years of age who have benign breast disease, especially those with atypical ductal or lobular hyperplasia. Lobular carcinoma in situ increases risk significantly, as do a family history of breast cancer in first-degree relatives and the presence of BRCA1 or BRCA2 mutations. Diet, exercise, and environmental factors play a very small role in overall risk. Mammographic breast density increases relative risk fivefold among women with the highest density, and breast cancer risk is two to three times greater in women with elevated serum levels of estradiol or testosterone. Multivariate risk models allow determination of composite relative risks and cumulative lifetime risk, although improved models for African American women are required. For postmenopausal women, newer risk models are being developed and validated that include age, breast density, race, ethnicity, family history of breast cancer, a previous breast biopsy, body mass index, age at onset of natural menopause, hormone therapy, and previous false-positive mammography. A simpler model that includes only age, breast cancer in first-degree relatives, and previous breast biopsy performs well for estrogen receptor-positive breast cancer in postmenopausal women. As many as 10 million women in the United States are at increased risk, and clinicians are obligated to identify these women and manage their risk appropriately.
Objective
One primary source of psychological distress in patients with cancer and their caregivers is uncertainty. However, the uncertainty trajectory and its relationship between older adults with ...advanced cancer and their caregivers have rarely been examined. This study describes the uncertainty trajectory in patient‐caregiver dyads, explores the effect of geriatric assessment (GA) intervention on trajectory, and examines the interdependent relationship of uncertainty.
Methods
This secondary analysis used longitudinal data from a national cluster‐randomized controlled trial examining a GA intervention compared to usual care. Participants completed the modified 9‐item Mishel Uncertainty in Illness Scale at enrollment, 4–6 weeks, 3 months, and 6 months. The dyadic growth model and cross‐lagged actor‐partner interdependence model were used.
Results
A total of 397 dyads (patient age M = 76.81 ± SD5.43; caregiver age M = 66.69 ± SD12.52) were included. Both had a trend of decreased uncertainty over time (b = −0.16, p < 0.01). There was a greater decrease in uncertainty among caregivers in the GA group than those in the usual care group (b = −0.46, p = 0.02). For both patients and caregivers, their past uncertainty was a significant predictor of their own current uncertainty (i.e., actor effect, p < 0.01). The individual's past uncertainty was a significant predictor of the other dyad member's current uncertainty (i.e., partner effect, p < 0.05), indicating an interdependent relationship between patient and caregiver uncertainty over time.
Conclusions
Findings suggest patient and caregiver function as a unit with uncertainty levels affecting each other. Future interventions could build on GA to address uncertainty for older patients with advanced cancer and caregivers.
To update an evidence-based technology assessment of chemoprevention strategies for breast cancer risk reduction. POTENTIAL INTERVENTIONS: Tamoxifen, raloxifene, aromatase inhibition, and ...fenretinide.
Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit.
A comprehensive, formal literature review was conducted for relevant topics. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO) prescribed technology assessment procedure was followed.
More weight was given to published randomized trials. BENEFITS/HARMS: A woman's decision regarding breast cancer risk reduction strategies is complex and will depend on the importance and weight attributed to information regarding both cancer- and noncancer-related risks and benefits.
For women with a defined 5-year projected breast cancer risk of > or= 1.66%, tamoxifen (at 20 mg/d for 5 years) may be offered to reduce their risk. Risk/benefit models suggest that greatest clinical benefit with least side effects is derived from use of tamoxifen in younger (premenopausal) women (who are less likely to have thromboembolic sequelae and uterine cancer), women without a uterus, and women at higher breast cancer risk. Data do not as yet suggest that tamoxifen provides an overall health benefit or increases survival. In all circumstances, tamoxifen use should be discussed as part of an informed decision-making process with careful consideration of individually calculated risks and benefits. Use of tamoxifen combined with hormone replacement therapy or use of raloxifene, any aromatase inhibitor or inactivator, or fenretinide to lower the risk of developing breast cancer is not recommended outside of a clinical trial setting. This technology assessment represents an ongoing process and recommendations will be updated in a timely matter.
The conclusions were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.
Vogel tackles an article by LaCroix et al describing the effect of lasofoxifene in reducing the incidence of breast cancer in post-menopausal women with osteoporosis. Lasofoxifene appears to ...represent an advance in the progression of pharmacological agents at their disposal, which can reduce both the risk of fractures in women with osteoporosis and the risk of breast cancer in postmenopausal women, possibly because it binds with high affinity to both estrogen receptors and ER-β. In contrast to lasofoxifene, however, raloxifene--the selective estrogen receptor modulator currently approved by the US Food and Drug Administration for treatment of osteoporosis--does not reduce the risk of nonvertebral fractures, perhaps because lasofoxifene decreases markers of bone turnover and improves spine bone mineral density more than does raloxifene at a dose of 60 mg, although the two agents have similar effects on total hip bone mineral density.
Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer-related bone loss in this cohort.
...Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers.
At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean +/- SE) 4.8% +/- 0.8% at the spine and 2.8% +/- 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% +/- 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% +/- 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% +/- 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups.
We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated.
The average age of the U.S. population is increasing, and cancer incidence increases with age. Both improved early detection of first malignancies and effective primary oncologic therapy have led to ...prolonged survival, and the risk of secondary malignancies has consequently increased. A few anatomic sites are at increased risk for second malignancies within the same organ: breast, colon and rectum, lung, head and neck (or upper aerodigestive malignancies), prostate, and the uterine cervix. Some of the cancers also incur a risk for a second malignancy at another anatomic site. In addition, there are well-described clinical genetic syndromes that, as unique clinical entities, predispose to second malignant tumors.
In this review, we focus on issues related to the risk of second malignancies among patients with primary breast, colon, lung and head and neck, prostate, and cervical cancers that comprise the most common sites of primary malignancy among patients in the United States. We review recent data related to both established and new screening strategies at these sites.
There is some evidence that screening will improve outcomes among patients who may develop second malignancies, although the data are limited. The optimal screening modalities and strategies to reduce mortality from second malignancies remain to be defined for most tumor sites.
The selective estrogen receptor modulators (SERM) tamoxifen and raloxifene can reduce the occurrence of breast cancer in high-risk women by 50%, but this U.S. Food and Drug Administration-approved ...prevention therapy is not often used. We attempted to identify genetic factors that contribute to variation in SERM breast cancer prevention, using DNA from the NSABP P-1 and P-2 breast cancer prevention trials. An initial discovery genome-wide association study identified common single-nucleotide polymorphisms (SNP) in or near the ZNF423 and CTSO genes that were associated with breast cancer risk during SERM therapy. We then showed that both ZNF423 and CTSO participated in the estrogen-dependent induction of BRCA1 expression, in both cases with SNP-dependent variation in induction. ZNF423 appeared to be an estrogen-inducible BRCA1 transcription factor. The OR for differences in breast cancer risk during SERM therapy for subjects homozygous for both protective or both risk alleles for ZNF423 and CTSO was 5.71.
The molecular etiology of breast cancer has proven to be remarkably complex. Most individual oncogenes are disregulated in only approximately 30% of breast tumors, indicating that either very few ...molecular alterations are common to the majority of breast cancers, or that they have not yet been identified. In striking contrast, we now show that 19 of 19 stage I breast tumors tested with the functional unscheduled DNA synthesis assay exhibited a significant deficiency of DNA nucleotide excision repair (NER) capacity relative to normal epithelial tissue from disease-free controls (n = 23). Loss of DNA repair capacity, including the complex, damage-comprehensive NER pathway, results in genomic instability, a hallmark of carcinogenesis. By microarray analysis, mRNA expression levels for 20 canonical NER genes were reduced in representative tumor samples versus normal. Significant reductions were observed in 19 of these genes analyzed by the more sensitive method of RNase protection. These results were confirmed at the protein level for five NER gene products. Taken together, these data suggest that NER deficiency may play an important role in the etiology of sporadic breast cancer, and that early-stage breast cancer may be intrinsically susceptible to genotoxic chemotherapeutic agents, such as cis-platinum, whose damage is remediated by NER. In addition, reduced NER capacity, or reduced expression of NER genes, could provide a basis for the development of biomarkers for the identification of tumorigenic breast epithelium.
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