Deborah J. Rhodes

Premature menopause or early menopause: Long-term health consequences

OBJECTIVE To review and summarize current evidence on the health consequences of premature menopause and early menopause. METHODS We reviewed existing literature and combined graphically some results from the Mayo Clinic Cohort Study of Oophorectomy and Aging. RESULTS Premature menopause or early menopause may be either spontaneous or induced. Women who experience premature menopause (before age 40 years) or early menopause (between ages 40 and 45 years) experience an increased risk of overall mortality, cardiovascular diseases, neurological diseases, psychiatric diseases, osteoporosis, and other sequelae. The risk of adverse outcomes increases with earlier age at the time of menopause. Some of the adverse outcomes may be prevented by estrogen treatment initiated after the onset of menopause. However, estrogen alone does not prevent all long-term consequences, and other hormonal mechanisms are likely involved. CONCLUSIONS Regardless of the cause, women who experience hormonal menopause and estrogen deficiency before reaching the median age of natural menopause are at increased risk for morbidity and mortality. Estrogen treatment should be considered for these women, but may not eliminate all of the adverse outcomes.

Increased cardiovascular mortality after early bilateral oophorectomy.

Objective: To investigate the mortality associated with cardiovascular diseases and the effect of estrogen treatment in women who underwent unilateral or bilateral oophorectomy before menopause. Design: We conducted a cohort study with long-term follow-up of women in Olmsted County, MN, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied the mortality associated with cardiovascular disease in a total of 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women. Results: Women who underwent unilateral oophorectomy experienced a reduced mortality associated with cardiovascular disease compared with referent women (hazard ratio [HR], 0.82; 95% CI, 0.67-0.99; P = 0.04). In contrast, women who underwent bilateral oophorectomy before age 45 years experienced an increased mortality associated with cardiovascular disease compared with referent women (HR, 1.44; 95% CI, 1.01-2.05; P = 0.04). Within this age stratum, the HR for mortality was significantly increased in women who were not treated with estrogen through age 45 years or longer (HR, 1.84; 95% CI, 1.27-2.68; P = 0.001) but not in women treated with estrogen (HR, 0.65; 95% CI, 0.30-1.41; P = 0.28; test of interaction, P = 0.01). Mortality was further increased after deaths associated with cerebrovascular causes were excluded. Conclusions: Bilateral oophorectomy performed before age 45 years is associated with increased cardiovascular mortality, especially with cardiac mortality. However, estrogen treatment may reduce this risk.

Dedicated Dual-Head Gamma Imaging for Breast Cancer Screening in Women with Mammographically Dense Breasts

PURPOSE To compare performance characteristics of dedicated dual-head gamma imaging and mammography in screening women with mammographically dense breasts. MATERIALS AND METHODS Asymptomatic women (n = 1007) who had heterogeneously or extremely dense breasts on prior mammograms and additional risk factors provided informed consent to enroll in an institutional review board-approved HIPAA-compliant protocol. Participants underwent mammography and gamma imaging after a 740-mBq (20-mCi) technetium 99m sestamibi injection. Reference standard (more severe cancer diagnosis or 12-month follow-up findings) was available for 936 of 969 eligible participants. Diagnostic yield, sensitivity, specificity, and positive predictive values (PPVs) were determined for mammography, gamma imaging, and both combined. RESULTS Of 936 participants, 11 had cancer (one with mammography only, seven with gamma imaging only, two with both combined, and one with neither). Diagnostic yield was 3.2 per 1000 (95% confidence interval [CI]: 1.1, 9.3) for mammography, 9.6 per 1000 (95% CI: 5.1, 18.2) for gamma imaging, and 10.7 per 1000 (95% CI: 5.8, 19.6) for both (P = .016 vs mammography alone). One participant had a second ipsilateral cancer detected with gamma imaging only. Prevalent screening gamma imaging demonstrated equivalent specificity relative to incident screening mammography (93% [861 of 925] vs 91% [840 of 925], P = .069). Of eight cancers detected with gamma imaging only, six (75%) were invasive (median size, 1.1 cm; range, 0.4-5.1 cm); all were node negative. The ratio of the number of patients with breast cancer per number of screening examinations with abnormal findings was 3% (three of 88) for mammography and 12% (nine of 73) for gamma imaging (P = .01). The number of breast cancers diagnosed per number of biopsies performed was 18% (three of 17) for mammography and 28% (10 of 36) for gamma imaging (P = .36). CONCLUSION Addition of gamma imaging to mammography significantly increased detection of node-negative breast cancer in dense breasts by 7.5 per 1000 women screened (95% CI: 3.6, 15.4). To be clinically important, gamma imaging will need to show equivalent performance at decreased radiation doses.

Molecular breast imaging: use of a dual-head dedicated gamma camera to detect small breast tumors.

OBJECTIVE Molecular breast imaging with a single-head cadmium zinc telluride (CZT) gamma camera has previously been shown to have good sensitivity for the detection of small lesions. To further improve sensitivity, we developed a dual-head molecular breast imaging system using two CZT detectors to simultaneously acquire opposing breast views and reduce lesion-to-detector distance. We determined the incremental gain in sensitivity of molecular breast imaging with dual detectors. SUBJECTS AND METHODS Patients with BI-RADS category 4 or 5 lesions < 2 cm that were identified on mammography or sonography and scheduled for biopsy underwent molecular breast imaging as follows: After injection of 740 MBq of technetium-99m ((99m)Tc) sestamibi, 10-minute craniocaudal and mediolateral oblique views of each breast were acquired. Blinded reviews were performed using images from both detectors 1 and 2 and images from detector 1 only (simulating a single-head system). Lesions were scored on a scale of 1-5; 2 or higher was considered positive. RESULTS Of the 150 patients in the study, 128 cancers were confirmed in 88 patients. Averaging the results from the three blinded readers, the sensitivity of dual-head molecular breast imaging was 90% (115/128), whereas the sensitivity from review of only single-head molecular breast imaging was 80% (102/128). The sensitivity for the detection of cancers < or = 10 mm in diameter was 82% (50/61) for dual-head molecular breast imaging and 68% (41/61) for single-head molecular breast imaging. On average, 13 additional cancers were seen on dual-head images and the tumor uptake score increased by 1 or more in 60% of the identified tumors. CONCLUSION Gains in sensitivity with the dual-head system molecular breast imaging are partially due to increased confidence in lesion detection. Molecular breast imaging can reliably detect breast lesions < 2 cm and dual-head molecular breast imaging can significantly increase sensitivity for subcentimeter lesions.

Molecular Breast Imaging: A New Technique Using Technetium Tc 99m Scintimammography to Detect Small Tumors of the Breast

OBJECTIVE To determine the sensitivity of molecular breast imaging (MBI) to detect small cancers of the breast. PATIENTS AND METHODS A cadmium-zinc-telluride gamma camera with a field of view of 20 × 20 cm was used. The detector elements were 2.5 × 2.5 mm. The gamma camera was mounted on a modified mammographic gantry. Between November 2001 and March 2004, we performed MBI on patients who were scheduled to undergo biopsy for a lesion suggestive of malignancy that was smaller than 2 cm on a mammogram. Patients were injected with 20 mCi of technetium Tc 99m sestamibi and underwent imaging immediately after injection. Using light pain-free compression, we obtained craniocaudal and mediolateral oblique views of each breast. RESULTS Of the 40 women included in the study, 26 had a total of 36 malignant lesions confirmed at surgery. Of these 36 lesions, 33 were detected by MBI (overall sensitivity, 92%). Of the 22 malignant lesions 1 cm or smaller in diameter, 19 were detected by MBI (sensitivity, 86%). Two patients had false-negative MBI results. Of the 14 malignant lesions larger than 1 cm in diameter, all were identified correctly by MBI. In 4 patients, MBI identified additional lesions not seen on mammography that were confirmed subsequently on magnetic resonance imaging and were true-positive cases at surgery. Three of these patients had lesions in the breast contralateral to the breast containing the initial mammographic finding suggestive of malignancy. Of 14 patients with no evidence of cancer at biopsy or surgery, 9 had true-negative (normal) scans and 5 had false-positive scans on MBI. False-positive results included benign fibroadenoma (2 patients), inflammatory fat necrosis (1 patient), benign breast parenchyma (1 patient), and complex sclerosing lesion (1 patient). CONCLUSION This prototype gamma camera system for MBI reliably detects malignant breast lesions smaller than 2 cm. Furthermore, we obtained the highest sensitivity (86%) yet reported for the detection of lesions smaller than 1 cm. These results suggest an important role for MBI, particularly for women in whom the sensitivity of mammography is reduced by the density of the breast parenchyma.

JOURNAL CLUB: Molecular Breast Imaging at Reduced Radiation Dose for Supplemental Screening in Mammographically Dense Breasts

OBJECTIVE. The purpose of this study was to assess the diagnostic performance of supplemental screening molecular breast imaging (MBI) in women with mammographically dense breasts after system modifications to permit radiation dose reduction. SUBJECTS AND METHODS. A total of 1651 asymptomatic women with mammographically dense breasts on prior mammography underwent screening mammography and adjunct MBI performed with 300-MBq (99m)Tc-sestamibi and a direct-conversion (cadmium zinc telluride) gamma camera, both interpreted independently. The cancer detection rate, sensitivity, specificity, and positive predictive value of biopsies performed (PPV3) were determined. RESULTS. In 1585 participants with a complete reference standard, 21 were diagnosed with cancer: two detected by mammography only, 14 by MBI only, three by both modalities, and two by neither. Of 14 participants with cancers detected only by MBI, 11 had invasive disease (median size, 0.9 cm; range, 0.5-4.1 cm). Nine of 11 (82%) were node negative, and two had bilateral cancers. With the addition of MBI to mammography, the overall cancer detection rate (per 1000 screened) increased from 3.2 to 12.0 (p < 0.001) (supplemental yield 8.8). The invasive cancer detection rate increased from 1.9 to 8.8 (p < 0.001) (supplemental yield 6.9), a relative increase of 363%, while the change in DCIS detection was not statistically significant (from 1.3 to 3.2, p =0.250). For mammography alone, sensitivity was 24%; specificity, 89%; and PPV3, 25%. For the combination, sensitivity was 91% (p < 0.001); specificity, 83% (p < 0.001); and PPV3, 28% (p = 0.70). The recall rate increased from 11.0% with mammography alone to 17.6% (p < 0.001) for the combination; the biopsy rate increased from 1.3% for mammography alone to 4.2% (p < 0.001). CONCLUSION. When added to screening mammography, MBI performed using a radiopharmaceutical activity acceptable for screening (effective dose 2.4 mSv) yielded a supplemental cancer detection rate of 8.8 per 1000 women with mammographically dense breasts.

Molecular Breast Imaging: Advantages and Limitations of a Scintimammographic Technique in Patients with Small Breast Tumors

Abstract:  Preliminary studies from our laboratory showed that molecular breast imaging (MBI) can reliably detect tumors <2 cm in diameter. This study extends our work to a larger patient population and examines the technical factors that influence the ability of MBI to detect small breast tumors. Following injection of 740 MBq Tc‐99m sestamibi, MBI was performed on 100 patients scheduled for biopsy of a lesion suspicious for malignancy that measured <2 cm on mammography or sonography. Using a small field of view gamma camera, patients were imaged in the standard mammographic views using light pain‐free compression. Subjective discomfort, breast thickness, the amount of breast tissue in the detector field of view, and breast counts per unit area were measured and recorded. Follow‐up was obtained in 99 patients; 53 patients had 67 malignant tumors confirmed at surgery. Of these, 57 of 67 were detected by MBI (sensitivity 85%). Sensitivity was 29%, 86%, and 97% for tumors <5, 6–10, and ≥11 mm in diameter, respectively. In seven patients, MBI identified eight additional mammographically occult tumors. Of 47 patients with no evidence of cancer at biopsy or surgery, there were 36 true negative and 11 false positive scans on MBI. MBI has potential for the regular detection of malignant breast tumors less than 2 cm in diameter. Work in progress to optimize the imaging parameters and technique may further improve sensitivity and specificity.

Increased Mortality for Neurological and Mental Diseases Following Early Bilateral Oophorectomy

Background: The effects of oophorectomy on brain aging remain uncertain. Methods: We conducted a cohort study with long-term follow-up of women in Olmsted County, Minn., USA, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied underlying and contributory causes of death in 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women. Results: Mortality for neurological or mental diseases was increased in women who underwent bilateral oophorectomy before age 45 years compared with referent women (hazard ratio = 5.24; 95% confidence interval = 2.02–13.6; p < 0.001). Within this age stratum, mortality was similar in women who were or were not treated with estrogen from the time of oophorectomy through age 45 years, and in women who had bilateral oophorectomy for prophylaxis or for treatment of a benign ovarian condition. Mortality was also increased in women who underwent unilateral oophorectomy before age 45 years without concurrent hysterectomy. Conclusions: Bilateral oophorectomy performed before age 45 years is associated with increased mortality for neurological or mental diseases.

Feasibility of Quantitative Pain Assessment in Outpatient Oncology Practice

PURPOSE Although physicians view failure to assess pain systematically as the most important barrier to outpatient cancer pain management, little is known about pain assessment in this setting. We sought to determine whether pain is routinely assessed and whether routine quantitative pain assessment is feasible in a busy outpatient oncology practice. PATIENTS AND METHODS We conducted a pre- and postintervention chart review of 520 randomly selected medical and radiation oncology patient visits at a community hospital-based private outpatient practice. The intervention consisted of training health assistants (HAs) to measure and document patient pain scores by using a visual analog scale. The main outcome measures included HA documentation of patient pain scores, quantitative and qualitative mention of pain in the physician note, and analgesic treatment before and after the intervention. RESULTS After the intervention, HA documentation of pain scores increased from 1% to 75.6% (P < .0001). Physician documentation increased from 0% to 4.8% for quantitative documentation (P < .01), and from 60.0% to 68.3% for qualitative documentation (not significant). Of all the patients, 23.1% reported significant pain. Subgroups with greater pain included patients actively receiving radiation treatments and patients with lung cancer. Of patients with significant pain, 28.2% had no mention of pain in the physician note and 47.9% had no documented analgesic treatment. CONCLUSION Quantitative pain assessment was virtually absent before our intervention but easily implemented and sustained in a busy outpatient oncology practice. Pain score collection identified a high prevalence of pain, patient subgroups at risk for pain, and a significant proportion of patients with pain that was neither evaluated nor treated by their oncologists.

Molecular breast imaging

Molecular breast imaging (MBI) is a new nuclear medicine technique that utilizes small semiconductor-based γ-cameras in a mammographic configuration to provide high-resolution functional images of the breast. Current studies with MBI have used Tc-99m sestamibi, which is an approved agent for breast imaging. The procedure is relatively simple to perform. Imaging can be performed within 5 min postinjection, with the breast lightly compressed between the two detectors. Images of each breast are acquired in the craniocaudal and mediolateral oblique projections facilitating comparison with mammography. Key studies have confirmed that MBI has a high sensitivity for the detection of small breast lesions. In patients with suspected breast cancer, MBI has an overall sensitivity of 90%, with a sensitivity of 82% for lesions less than 10 mm in size. Sensitivity was lowest for tumors less than 5 mm in size. Tumor detection does not appear to be dependent on tumor type, but rather on tumor size. Studies using MBI and breast-specific γ-imaging have shown that these methods have comparable sensitivity to breast MRI. A large clinical trial compared MBI with screening mammography in over 1000 women with mammographically dense breast tissue and increased risk of breast cancer and showed that MBI detected two-to three-times more cancers than mammography. In addition, MBI appears to have slightly better specificity than mammography in this trial. MBI provides high-resolution functional images of the breast and its potential applications range from evaluation of the extent of disease to a role as an adjunct screening technique in certain high-risk populations. MBI is highly complementary to existing anatomical techniques, such as mammography, tomosynthesis and ultrasound.