Breast Neoplasms: Col NF

Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, Morrow M, Runowicz C, Pritchard KI, Hagerty K, Arun B, Garber J, Vogel VG, Wade JL, Brown P, Cuzick J, Kramer BS, Lippman SM, Anonymous00092. · Cancer Policy and Clinical Affairs, 2318 Mill Rd, Suite 800, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #19470930 No free full text.

Abstract: PURPOSE To update the 2002 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS A literature search identified relevant randomized trials published since 2002. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. An expert panel reviewed the literature and developed updated consensus guidelines. Results Seventeen articles met inclusion criteria. In premenopausal women, tamoxifen for 5 years reduces the risk of BC for at least 10 years, particularly estrogen receptor (ER) -positive invasive tumors. Women < or = 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist post-treatment across all ages. In postmenopausal women, raloxifene and tamoxifen reduce the risk of ER-positive invasive BC with equal efficacy. Raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in BC risk from either agent translates into reduced BC mortality. Recommendations In women at increased risk for BC, tamoxifen (20 mg/d for 5 years) may be offered to reduce the risk of invasive ER-positive BC, with benefits for at least 10 years. In postmenopausal women, raloxifene (60 mg/d for 5 years) may also be considered. Use of aromatase inhibitors, fenretinide, or other selective estrogen receptor modulators to lower BC risk is not recommended outside of a clinical trial. Discussion of risks and benefits of preventive agents by health providers is critical to patient decision making.

Col NF, Chlebowski RT. · Center for Outcomes Research and Evaluation, Maine Medical Center, Portland, ME 04101, USA. · Menopause. · Pubmed #18596602 No free full text.

Abstract: Decision making about menopausal therapies is complex because of the number of clinical factors that must be considered. Menopausal hormone therapy can relieve the vasomotor symptoms of menopause, but the most common preparation, combination estrogen and progesterone, increases the risk of breast cancer. Both tamoxifen and raloxifene can reduce the risk of developing invasive breast cancer, but the adverse effects of these drugs differ substantially. Risk models have been built to identify women at high risk for developing breast cancer, but their application in clinical practice has been develop disappointingly low. We propose an approach for identifying and managing menopausal women at high risk for breast cancer that can be readily implemented in clinical practice. The first step is to identify women at sufficiently high risk for breast cancer to merit treatment. For women aged 45 or older, the presence of one or more first-degree relatives with breast cancer and one or more previous breast biopsies will identify those whose 5-year risk is 2% or higher. For women 55 years or older, the presence of either one of these risk factors is sufficient. Any woman with a family history of breast cancer should be assessed as to whether she is likely to carry a BRCA mutation and referred for genetic counseling and possible genetic testing. Decisions about treatment options should be based on the presence or absence of bothersome vasomotor symptoms, an intact uterus, and risk factors for cardiovascular disease. A simple algorithm is presented to streamline identification and management of menopausal women at high risk for breast cancer.

Chlebowski RT, Kim JA, Col NF. · Harbor-UCLA Research and Education Institute, Torrance 90502, USA. · Semin Oncol. · Pubmed #14663778 No free full text.

Abstract: Vasomotor symptoms associated with menopause or cancer therapies represent an increasingly common problem for breast cancer survivors given the increasing use of ovarian suppression in premenopausal women and aromatase inhibitors in postmenopausal women. Although estrogen and/or progestin effectively reduce vasomotor symptoms, a recent Women's Health Initiative (WHI) randomized trial identified an unfavorable risk/benefit balance on life-threatening diseases, including increased breast cancer, for combined estrogen plus progestin use in otherwise healthy postmenopausal women. As a result, use of menopausal hormone therapy (MHT) for chronic disease risk reduction in any population cannot be supported. In addition, the safety of estrogen and/or progestin regarding risk of recurrence or new cancer development in breast cancer survivors has not been demonstrated. For vasomotor symptoms in this population, neuroendocrine agents, including selective seratonin reuptake inhibitors (SSRIs) or gabapentin, are reasonable choices with substantial impact on hot flashes and moderate toxicity profiles. When rigorously evaluated, most other nonhormonal pharmacologic and herbal interventions have been found to have either modest or no efficacy and/or limiting toxicity. In breast cancer survivors even local vulvar/vaginal symptoms are best treated by nonhormone products since drug absorption with systemic estrogen-like effects has been reported. Estrogen/progestin use in breast cancer survivors should be considered only for women with severe vasomotor symptoms refractory to other approaches after extensive informed decision-making including review of current Food and Drug Administration labeling concerns with use limited to the lowest dose and shortest duration possible.

Col NF. · Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · Med Decis Making. · Pubmed #14570302 No free full text.

Abstract: Screening for genetic susceptibility provides new opportunities for preventing common diseases, but whether such screening will result in substantial costs or savings is unclear. Cost-effectiveness analyses (CEAs) provide a theoretical framework for guiding clinical decisions about genetic tests. However, CEAs have been largely irrelevant in informing policy, clinical decisions, or patient demand concerning these genetic tests. Genetic tests have often proceeded directly from development and preliminary validation into clinical practice, with little understanding of their clinical, economic, and psychosocial implications. Using screening for BRCA mutations as an example, the accuracy of the tests and the effectiveness of many interventions among those who screen positive remain in question. CEAs do not seem to have played an important role in identifying whom to offer genetic testing nor how to manage those found to carry the gene marker. Credible CEAs are needed to provide guidance about screening decisions.

Col NF, Hirota LK, Orr RK, Erban JK, Wong JB, Lau J. · Division of General Medicine and Decision Systems Group, Brigham and Women's Hospital and Harvard Medical School, Chestnut Hill, MA 02467, USA. · J Clin Oncol. · Pubmed #11304788 No free full text.

Abstract: PURPOSE: Hormone replacement therapy (HRT) is typically withheld from women with breast cancer because of concern that it might increase the risk of recurrence. The purpose of this study was to quantify the risk of recurrent breast cancer associated with HRT among breast cancer survivors. METHODS: We performed a systematic literature review through May 1999, calculating the relative risk (RR) of breast cancer recurrence in each study by comparing the number of recurrences in the HRT group to those in the control group. In studies that did not contain a control group, we constructed one by estimating the expected number of recurrences based on data from the Early Breast Cancer Trialists' Collaborative Group, adjusting for nodal status and disease-free interval. RRs across all studies were combined using random-effects models. RESULTS: Of the 11 eligible studies, four had control groups and included 214 breast cancer survivors who began HRT after a mean disease-free interval of 52 months. Over a mean follow-up of 30 months, 17 of 214 HRT users experienced recurrence (4.2% per year), compared with 66 of 623 controls (5.4% per year). HRT did not seem to affect breast cancer recurrence risk (RR = 0.64, 95% confidence interval [CI], 0.36 to 1.15). Including all 11 studies in the analyses (669 HRT users), using estimated control groups for the seven uncontrolled trials, the combined RR was 0.82 (95% CI, 0.58 to 1.15). CONCLUSION: Although our analyses suggest that HRT has no significant effect on breast cancer recurrence, these findings were based on observational data subject to a variety of biases.

Orr RK, Hoehn JL, Col NF. · Department of Surgery, The Marshfield Clinic, Wis, USA. · Arch Surg. · Pubmed #10401830 links to  free full text

Abstract: HYPOTHESIS: Performance of sentinel node biopsy (SNB) instead of full axillary lymph node dissection (ALND) by inexperienced surgeons will lead to understaging of some women with breast cancer and increased costs. DESIGN: A decision analysis model was used to investigate the implications of SNB vs. full ALND during the learning phase (60-80 procedures). This model simulates a randomized trial of 10000 women in each arm. Data regarding the learning curve were obtained from published series. MAIN OUTCOME MEASURES: Percentage of women with inaccurate staging of their breast cancer, overall survival, quality-adjusted survival, and potential costs of SNB vs ALND. RESULTS: Performance of SNB instead of ALND results in inability to locate a sentinel node in 38% of attempts during the learning phase (compared with 10% in later cases) and understaging in 12% of patients during the learning phase (compared with 0% in later cases). This understaging is associated with a small decrement in survival (1%-2%) and an increased risk of axillary recurrence. Sentinel node biopsy is cost-effective only when the ability to detect sentinel nodes exceeds 80%; and the cost of SNB is less than 50% of the cost of ALND. CONCLUSIONS: To ensure accurate staging of patients with breast cancer, all surgeons should perform full ALND while learning SNB techniques. Only after documentation of accuracy of SNB (sensitivity >90%) should full ALND be omitted for women with negative sentinel nodes.

Matloff ET, Shannon KM, Moyer A, Col NF. · Cancer Genetic Counseling, Yale Cancer Center, Yale School of Medicine,New Haven, CT 06520, USA. · J Cancer Educ. · Pubmed #17570802 No free full text.

Abstract: BACKGROUND: Menopausal women with a family history of breast cancer have several treatment options, including tamoxifen, raloxifene, and hormone therapy. This complex decision should be based on each woman's risk to develop breast cancer, menopausal symptoms, preferences, and risks for other conditions. Current models in use do not include pedigree analysis, personalized risk assessment, or genetic testing in this process. METHODS: We created a personalized risk assessment and genetic counseling intervention for healthy women with a first-degree relative with breast cancer. Participants were given a personalized risk assessment for breast cancer, heart disease, osteoporosis, and uterine cancer based on family history and personal health data. COUNSELING MODEL: The effectiveness of this novel genetic counseling intervention was demonstrated in a randomized trial and these results are published elsewhere. The framework for this counseling model, with case examples from the clinical trial, is outlined in this article. CONCLUSIONS: As more menopausal therapies are developed, each with its own risks and benefits, it will become even more critical to have a personalized counseling model for use in this process. Clinicians and educators can utilize the framework presented here for counseling women with a family history of breast cancer.

Matloff ET, Moyer A, Shannon KM, Niendorf KB, Col NF. · Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut 06520, USA. · J Womens Health (Larchmt). · Pubmed #16999640 No free full text.

Abstract: BACKGROUND: Women with a family history of breast cancer have several menopausal therapy options, including tamoxifen, hormone therapy (HT), alternative medications, or no treatment. This complex decision should be based on each woman's risk to develop breast cancer, menopausal symptoms, preferences, and risks for other conditions. The authors determined the effects of a personalized risk assessment and genetic counseling intervention on knowledge, risk perception, and decision making in a group of healthy women who had a first-degree relative with breast cancer. METHODS: Forty-eight cancer-free menopausal women age > or =40 years who had at least one first-degree relative with breast cancer were randomized to a genetic counseling intervention or control. Intervention participants were given a personalized risk assessment for breast cancer, heart disease, osteoporosis, and uterine cancer based on family history and personal health data. Knowledge, risk perception, and medication usage were measured at baseline, 1 month, and 6 months. RESULTS: Knowledge was higher in the intervention group at both follow-up time points postintervention. Perceived risk for developing breast cancer was significantly lower and more accurate in the intervention group at 1 and 6 months postintervention than at baseline, as was perceived risk of developing heart disease. Although the counseling intervention did affect both knowledge and risk perception, overall, both groups were reluctant to take any form of menopausal therapy. CONCLUSIONS: A personalized risk assessment and genetic counseling intervention improves patient knowledge and risk perception; however, it is unclear that the intervention influenced menopausal treatment decisions.

Col NF, Kim JA, Chlebowski RT. · Brown Medical School, Providence, Rhode Island, USA. · Breast Cancer Res. · Pubmed #15987460 links to  free full text

Abstract: INTRODUCTION: Menopausal hormone therapy (HT) is typically withheld from breast cancer survivors because of concerns about risk for recurrence. Our objectives were to estimate the effects of HT on recurrence in breast cancer survivors and to examine the reliability of these estimates. METHODS: In a systematic review of the literature we identified all reports of HT use in breast cancer survivors that included comparison groups. Study design features that might affect selection of participants, detection of recurrence, and manuscript publication were assessed. The relative risks for breast cancer recurrence associated with HT were combined with random effects models. RESULTS: Two randomized and eight observational studies included 1,316 breast cancer survivors who used HT and 2,839 nonusers. In the observational studies, HT users were younger and more commonly node negative; only two reported balanced restaging for HT and control groups. Randomized trials suggest that HT increased the risk for recurrence (relative risk 3.41, 95% confidence interval 1.59-7.33), whereas observational studies suggest that HT decreased this risk (relative risk 0.64, 95% confidence interval 0.50-0.82). CONCLUSION: Results from observational studies of HT conducted in breast cancer survivors are discrepant with results from randomized trials. Observational studies of HT use in breast cancer survivors have design limitations that cannot be controlled for using standard statistical methods. Therefore, the randomized clinical trial data provide the only reliable estimates of the effect of HT use on recurrence risks in breast cancer survivors.

Col NF, Duffy C, Landau C. · Department of Medicine, Brown Medical School and Rhode Island Hospital, MPB-1, 593 Eddy St., Providence, Rhode Island 02903, USA. · Health Serv Res. · Pubmed #15960690 links to  free full text

This publication has no abstract.

Braithwaite RS, Chlebowski RT, Lau J, George S, Hess R, Col NF. · Section of Clinical Systems Modeling, Division of General Internal Medicine, Department of Medicne, University of Pittsburgh, Pittsburgh, PA 15213, USA. · J Gen Intern Med. · Pubmed #14687281 links to  free full text

Abstract: OBJECTIVE: Tamoxifen reduces the risk of developing breast cancer but also affects the risks of certain vascular and neoplastic events. Our purpose was to estimate the effects of tamoxifen on potentially life-threatening vascular and neoplastic outcomes. DESIGN: Random effects meta-analysis of published randomized controlled trials. PATIENTS: Participants in all trials in which a treatment arm that included tamoxifen was compared to a similar control arm. Breast cancer risk reduction and treatment trials were included. INTERVENTIONS: Tamoxifen at variable dose and duration. MEASUREMENTS AND MAIN RESULTS: Thirty-two trials (52,929 patients) reported one or more outcomes of interest. Tamoxifen was associated with significantly increased risks of endometrial cancer (relative risk [RR] 2.70; 95% CI, 1.94 to 3.75), gastrointestinal cancers (RR 1.31; 95% CI, 1.01 to 1.69), strokes (RR 1.49; 95% CI, 1.16 to 1.90), and pulmonary emboli (RR 1.88; 95% CI, 1.77 to 3.01). Tamoxifen had no effect on secondary malignancies other than endometrial and gastrointestinal cancers (RR 0.96; 95% CI, 0.81 to 1.13). In contrast, tamoxifen significantly decreased myocardial infarction deaths (RR 0.62; 95% CI, 0.41 to 0.93) and was associated with a statistically insignificant decrease in myocardial infarction incidence (RR 0.90; 95% CI, 0.66 to 1.23). Postmenopausal women had greater risk increases for neoplastic outcomes. CONCLUSIONS: This meta-analysis of randomized trials found tamoxifen use to be significantly associated with several neoplastic and vascular outcomes. Consideration of tamoxifen use requires balance of potential benefits and risks.

Col NF, Goldberg RJ, Orr RK, Erban JK, Fortin JM, Chlebowski RT. · · Med Decis Making. · Pubmed #12365480 No free full text.

Abstract: The authors estimate tamoxifen's impact on life expectancy among healthy women. A Markov model compared the effects of 5 years of tamoxifen on survival among 50-year-old postmenopausal women. Scenarios were explored using alternative assumptions with regard to tamoxifen's long-term effects on breast and endometrial cancer. Postmenopausal women without a uterus had substantial life expectancy gains from tamoxifen (1 to 4 months), whereas women with a uterus had such gains only if they were at a very high breast cancer risk. If tamoxifen's impact on endometrial cancer persists after treatment is discontinued, women at high risk for endometrial cancer have life expectancy losses from tamoxifen unless they are at a very high risk for breast cancer. The authors conclude that tamoxifen use among postmenopausal women is associated with substantial life expectancy gains. However, this benefit is modulated in women at increased endometrial cancer risk and depends on assumptions concerning tamoxifen's lingering effects on breast and endometrial cancer.

Orr RK, Col NF, Kuntz KM. · Department of Surgery, Marshfield Clinic, Wis., USA. · Surgery. · Pubmed #10486611 No free full text.

Abstract: PURPOSE: The purpose of this study was to examine the cost-effectiveness of immediate axillary lymph node dissection (ALND) in estrogen receptor-positive women with clinically negative nodes. METHODS: We constructed a Markov model comparing hypothetical cohorts of postmenopausal women who were estrogen receptor positive with clinically negative axillae. The women underwent immediate ALND or watchful waiting, with ALND performed only for those patients developing palpable axillary nodes. Recurrence risks, chemotherapeutic benefits, and treatment costs were estimated from the published literature. The main outcome measures were quality-adjusted survival and incremental cost per quality-adjusted life-year (QALY). RESULTS: For 55-year-old women with palpable (3 cm) tumors, immediate ALND results in improved survival (10.3 versus 10.05 QALYs) and a cost-effectiveness ratio of $36,700 per QALY, if chemotherapy is given to those with histologically positive lymph nodes. The benefits of ALND are greatest for younger women with larger palpable tumors. Because of the lower risk of nodal metastases, patients with 1-cm nonpalpable tumors experience minimal benefit at markedly higher incremental costs ($308,000 per QALY). If chemotherapy will not be given to patients with histologically positive lymph nodes because of a patient's or a physician's wishes, then there is no benefit to immediate ALND in any patient subgroup. CONCLUSION: When the results of ALND are used to guide postoperative decisions, immediate ALND results in considerable benefit at a reasonable cost for most women with palpable tumors. Because the benefits are lower in patients with nonpalpable tumors, ALND should not be considered mandatory for that subgroup. Decisions for ALND should be based on patient age, tumor size and palpability, individual patient preferences, the likelihood of receiving postoperative chemotherapy, and other prognostic factors.

Col NF, Pauker SG, Goldberg RJ, Eckman MH, Orr RK, Ross EM, Wong JB. · Department of Medicine, Tupper Research Institute, New England Medical Center and Tufts University School of Medicine, Boston, Mass 02111, USA. · Arch Intern Med. · Pubmed #10399897 links to  free full text

Abstract: BACKGROUND: Alendronate sodium and raloxifene hydrochloride were recently approved for the prevention of postmenopausal osteoporosis, but data on their clinical efficacy are limited. We compared these drugs with hormone replacement therapy (HRT) to help women and physicians guide postmenopausal treatment decisions. OBJECTIVE: To help physicians understand how they can best help women choose the most beneficial therapy after menopause based on their individual risk profile. METHODS: We developed a decision analytic Markov model to compare the effects of alendronate therapy, raloxifene therapy, and HRT on risks of hip fracture, coronary heart disease (CHD), breast cancer, and life expectancy. Regression models linked individual risk factors to future disease risks and were modified by drug effects on bone density, lipid levels, and associated breast cancer effects. RESULTS: Hormone replacement therapy, alendronate therapy, and raloxifene therapy have similar predicted efficacies in preventing hip fractures (estimated relative risk, 0.57, 0.54, and 0.58, respectively). Hormone replacement therapy should be more than 10 times more effective than raloxifene therapy in preventing CHD, but raloxifene therapy may not induce breast cancer. Women at low risk for hip fracture, CHD, and breast cancer do not benefit significantly from any treatment. Among women at average risk, HRT was preferred unless raloxifene therapy could reduce the risk of breast cancer by at least 66%, compared with a 47% increase for HRT. Women at high risk for CHD benefit most from HRT; women at high risk for breast cancer but low risk for CHD benefit most from raloxifene therapy, but only if it lowers the risk of breast cancer. CONCLUSION: Because of significant differences in the impact of these drugs, treatment choice depends on an individual woman's risk for hip fracture, CHD, and breast cancer.