Stephanie L. Hines

Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer

PURPOSE Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. PATIENTS AND METHODS Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. RESULTS A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. CONCLUSION Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.

Breast cancer survivors and vitamin D: A review

Recent evidence has suggested a role for vitamin D in breast cancer prevention and survival. Studies have reported an inverse relation between vitamin D intake and the risk of breast cancer, improvements in survival after a diagnosis of breast cancer in women with higher levels of vitamin D, and vitamin D insufficiency in up to 75% of women with breast cancer. Preclinical data have indicated that vitamin D affects up to 200 genes that influence cellular proliferation, apoptosis, angiogenesis, terminal differentiation of normal and cancer cells, and macrophage function. Vitamin D receptors have been found in up to 80% of breast cancers, and vitamin D receptor polymorphisms have been associated with differences in survival. Although ongoing studies have investigated a possible link between adequate levels of vitamin D and improved cancer prognosis, breast cancer survivors may derive additional, non-cancer-related benefits from adequate vitamin D levels, including improvements in bone mineral density, quality of life, and mood. Maintaining adequate vitamin D stores is recommended for breast cancer survivors throughout their lifetime.

The Role of Mammography in Male Patients With Breast Symptoms

OBJECTIVE To determine the contribution of mammography to the comprehensive clinical evaluation of men with breast symptoms. PATIENTS AND METHODS We retrospectively reviewed the records of all men who underwent mammography between January 1, 2001, and December 31, 2004, at the Mayo Clinic In Jacksonville, Fla. Medical history, mammographic findings, and breast cancer diagnoses were assessed. RESULTS A total of 198 men had 212 mammograms. Nine mammograms (from 9 different men) (4%) showed suspicious findings. Eight men underwent biopsy, which yielded a breast cancer diagnosis in 2 (1%). Of the 212 mammograms, 203 (96%) showed benign findings, including gynecomastia on 132 (62%). One patient with a benign-appearing mammogram later underwent breast biopsy, and malignant disease was diagnosed. All the men with breast cancer had a dominant mass on clinical examination and other findings suggestive of breast cancer. Of the 132 mammograms showing gynecomastia, 110 (83%) were from men who had taken predisposing medications or who had predisposing medical conditions. CONCLUSIONS Mammography added little information to the initial patient evaluation. Breast cancer may be suspected by the presence of a dominant mass. Gynecomastia can be predicted on the basis of the patients symptoms or preexisting condition. Patients with suspicious findings on examination warrant appropriate clinical management regardless of mammographic findings. Mammography in men may be of benefit only for image guidance of percutaneous biopsy of a suspicious mass.

Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy

BACKGROUND Postmenopausal women with osteoporosis/osteopenia are at increased risk of fracture. Aromatase inhibitors further increase bone loss in these patients. This study evaluates whether zoledronic acid prevents the bone loss expected when these patients initiate letrozole. PATIENTS AND METHODS Postmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a bone mineral density (BMD) T-score <-2.0 were given letrozole 2.5mg/vitamin D 400 international units daily, calcium 500mg twice daily, and 4mg zoledronic acid every 6 months. The BMD was assessed at baseline and 1 year. The primary endpoint was the mean change in lumbar spine (LS) BMD at 1 year. RESULTS Forty-six patients completed 1 year of treatment. LS BMD increased by 2.66% (p=0.01), femoral neck (FN) by 4.81% (p=0.01), and any measured endpoint by 4.55% (p=0.0052). CONCLUSIONS Zoledronic acid prevents bone loss in postmenopausal women with osteoporosis/osteopenia starting letrozole and is associated with improvements in BMD.

Ductal carcinoma in situ of the breast

Ductal carcinoma in situ (DCIS) of the breast represents a complex, heterogeneous pathologic condition in which malignant epithelial cells are confined within the ducts of the breast without evidence of invasion. The increased use of screening mammography has led to a significant shift in the diagnosis of DCIS, accounting for approximately 27% of all newly diagnosed cases of breast cancer in 2011, with an overall increase in incidence. As the incidence of DCIS increases, the treatment options continue to evolve. Consistent pathologic evaluation is crucial in optimizing treatment recommendations. Surgical treatment options include breast-conserving surgery (BCS) and mastectomy. Postoperative radiation therapy in combination with breast-conserving surgery is considered the standard of care with demonstrated decrease in local recurrence with the addition of radiation therapy. The role of endocrine therapy is currently being evaluated. The optimization of diagnostic imaging, treatment with regard to pathological risk assessment, and the role of partial breast irradiation continue to evolve.

5‐year follow‐up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial

Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5‐year follow‐up results.

Phase II Evaluation of Desipramine for the Treatment of Hot Flashes

PURPOSE Newer antidepressants with serotonergic effects reduce hot flashes significantly better than placebo. This pilot study was designed to test the efficacy of desipramine, an older antidepressant targeting norepinephrine, in women desiring therapy for hot flashes and to evaluate the toxicity of desipramine. PATIENTS AND METHODS In this nonrandomized trial, eligible women were required to have reported >/= 14 bothersome hot flashes per week for >/= 1 month. After an Initials baseline week in which no study medication was taken, participants started with desipramine 25 mg daily, which was titrated to100 mg daily by week 5. The primary endpoint was change from baseline in hot flash frequency and hot flash score. Statistical methods involved paired t tests for continuous variables and Fisher exact tests for categoric variables. RESULTS Twenty-six patients were enrolled on this study between March 2004 and November 2005. The decrease in mean hot flash frequency over 4 weeks of treatment was 23%, with a 31% reduction in hot flash scores. Seven patients (30%) withdrew early because of toxicities consisting of insomnia, nausea, headaches, and/or feeling frightened. CONCLUSION Desipramine did not reduce hot flashes beyond the 25%-30% reduction that would be expected with placebo, based on previous work. Therefore, data from this trial do not support further study of this agent for treatment of hot flashes. It is of physiologic interest that this older antidepressant, classified as a tricyclic, did not achieve a clinically significant reduction in hot flash scores in this pilot trial.

Observed frequency and challenges of variant reclassification in a hereditary cancer clinic

PurposeEfforts have been made by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology to make variant classification more uniform, but many limitations remain. Reclassification of a variant of uncertain significance (VUS) is expected, but other more certain calls, like pathogenic or benign, can also be reclassified once additional information is gathered. Variant reclassification can create difficult circumstances for both patients and clinicians.MethodsRetrospective review of all variant reclassifications in genes associated with hereditary cancer syndromes at one clinic between September 2013 and February 2017 was completed. All variant reclassifications were completed and reported by the original testing laboratory.ResultsA total of 1,103 hereditary cancer tests were ordered. Fewer than 5% (40/1,103) of the initial reports were updated during that time period. Most reclassifications (29/40) were downgrades of VUS to likely benign. Only three reclassifications could potentially alter medical management.ConclusionThe majority of variant reclassifications do not impact medical management. Upgrading a variant call to pathogenic could be important for a patient’s care and shows the importance of open communication between laboratories and clinicians. A variant downgrade from pathogenic can be a significant reclassification as well, especially if prophylactic surgery has been completed.

The ability of preoperative magnetic resonance imaging to predict actual pathologic tumor size in women with newly diagnosed breast cancer.

Abstract #4018 Background: Preoperative breast magnetic resonance imaging (MRI) has been shown to identify occult breast disease in women with newly diagnosed breast cancer. We sought to determine the accuracy of MRI in predicting the actual pathologic tumor size in women with newly diagnosed breast cancer.
 Methods: Preoperative breast MRI was reviewed in 460 women with newly diagnosed breast cancer. The size in terms of maximum tumor dimension, of 476 incident breast cancers on MRI were recorded and correlated with the actual pathologic size upon surgical resection. The correlation of size from MRI to pathology was determined. The size discrepancy was analyzed in relation to tumor size and histology.
 Results: MRI demonstrated 476 breast cancers (460 in the ipsilateral breast and 16 with concurrent contralateral breast cancer). Median age was 62 with a range of 25 to 91. The T stages of the population included T0 in 19% of the women, 60% had T1 lesions, 18% had T2 lesions and 3% were T3 or T4. The histology consisted of DCIS alone in 20%, infiltrating ductal in 74% and infiltrating lobular in 6%. Pre-operative MRI was unable to define an enhancing lesion usually due to hematoma following core needle biopsy in 9.8% (47/476). MRI described the size of the incident lesion in 90% (429/476). The mean difference in size between the preoperative MRI and the actual pathologic size for the entire group was 2.4 mm. MRI underestimated tumor size in only 3% of cases. The mean difference according to T stage and histology between MRI and actual pathologic size is listed in Table 1. The percentage of difference between MRI size and pathologic size for the entire group is presented in Table 2.
 Discussion: The mean difference in tumor size estimated by preoperative MRI in women with newly diagnosed breast cancer was within 5 mm of the actual pathologic size in 68% of patients. MRI was accurate in predicting T stage with no significant difference in relation to histology or T stage. This analysis further clarifies the role of preoperative MRI in surgical and treatment planning. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4018.

Physician interpretation of variants of uncertain significance

A growing number of physicians will interact with genetic test results as testing becomes more commonplace. While variants of uncertain significance can complicate results, it is equally important that physicians understand how to incorporate these results into clinical care. An online survey was created to assess physician self-reported comfort level with genetics and variants of uncertain significance. Physicians were asked to respond to three case examples involving genetic test results. The survey was sent to 488 physicians at Mayo Clinic FL on 8/16/2017. Physicians from all specialties were invited to participate. A total of 92 physicians responded to the survey. Only 13/84 (14.6%) responded to all three case examples with the answer deemed “most correct” by review of literature. Physicians that specialized in cancer were more likely to answer questions appropriately (P = .02). Around half (39/84) of the physicians incorrectly defined a variant of uncertain significance (VUS). Over 75% made a recommendation for genetic testing that was not warranted. Many physicians have never received formal genetics training; however, they will be expected to provide an accurate explanation of the genetic test results and subsequent evidence-based medical management recommendations. These results demonstrate that a substantial proportion of physicians lack a true understanding of the implications a VUS. Utilization of supplemental genetics training programs coupled with increase awareness of genetic services may help to improve patient care.