Surgery In Postmenopausal Women Research Articles

Dose-dependent change in biomarkers during neoadjuvant endocrine therapy with fulvestrant: results from NEWEST, a randomized Phase II study

NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors) is the first study to compare biological and clinical activity of fulvestrant 500 versus 250 mg in the neoadjuvant breast cancer setting. We hypothesized that fulvestrant 500 mg may be superior to 250 mg in blocking estrogen receptor (ER) signaling and growth. A multicenter, randomized, open-label, Phase II study was performed to compare fulvestrant 500 mg (500 mg/month plus 500 mg on day 14 of month 1) versus fulvestrant 250 mg/month for 16 weeks prior to surgery in postmenopausal women with ER+ locally advanced breast cancer. Core biopsies at baseline, week 4, and surgery were assessed for biomarker changes. Primary endpoint: change in Ki67 labeling index (LI) from baseline to week 4 determined by automated computer imaging system (ACIS). Secondary endpoints: ER protein expression and function; progesterone receptor (PgR) expression; tumor response; tolerability. ER and PgR were examined retrospectively using the H score method. A total of 211 patients were randomized (fulvestrant 500 mg: n = 109; 250 mg: n = 102). At week 4, fulvestrant 500 mg resulted in greater reduction of Ki67 LI and ER expression versus 250 mg (-78.8 vs. -47.4% [p < 0.0001] and -25.0 vs. -13.5% [p = 0.0002], respectively [ACIS]); PgR suppression was not significantly different (-22.7 vs. -17.6; p = 0.5677). However, H score detected even greater suppression of ER (-50.3 vs. -13.7%; p < 0.0001) and greater PgR suppression (-80.5 vs. -46.3%; p = 0.0018) for fulvestrant 500 versus 250 mg. At week 16, tumor response rates were 22.9 and 20.6% for fulvestrant 500 and 250 mg, respectively, with considerable decline in all markers by both ACIS and H score. No detrimental effects on endometrial thickness or bone markers and no new safety concerns were identified. This provides the first evidence of greater biological activity for fulvestrant 500 versus 250 mg in depleting ER expression, function, and growth.

Risk Factors for Neurocognitive Dysfunction After Cardiac Surgery in Postmenopausal Women

Women are at higher risk than men for neurologic complications from cardiac operations. This study identified risk factors for neurocognitive dysfunction after cardiac operations in elderly women. One hundred thirteen postmenopausal women undergoing primary coronary artery bypass grafting, with or without valve operation, underwent psychometric testing and neurologic evaluation the day before operation and 4 to 6 weeks postoperatively. Risk factors assessed for neurologic complications included atherosclerosis of the ascending aorta and apolipoprotein epsilon4 genotype. Postoperative neurocognitive dysfunction was defined as the composite end point of a one standard deviation decrement from baseline on two or more psychometric tests or a new neurologic deficit. Neurocognitive dysfunction was present in 25% of the women 4 to 6 weeks postoperatively. Women with a neurocognitive deficit tended to be older than those without a deficit (72.1 +/- 8.1 vs 69.4 +/- 8.9 years, p = 0.144) and were more likely to have mild atherosclerosis of the ascending aorta, a history of congestive heart failure, longer duration of cardiopulmonary bypass (CPB) and aortic cross-clamping, lower nadir blood pressure during CPB, higher rates of postoperative atrial fibrillation, and longer postoperative hospitalization. Mild atherosclerosis of the ascending aorta, duration of CPB, duration of aortic cross-clamping (p = 0.051), and length of postsurgical hospitalization were independently associated with postoperative neurocognitive dysfunction. Mild atherosclerosis of the ascending aorta, duration of CPB, aortic cross-clamping time, and length of hospitalization, but not apolipoprotein epsilon4 genotype, identified risk for neurocognitive dysfunction after cardiac operation in postmenopausal women.

Health-related Quality of Life Following Coronary Artery Bypass Graft Surgery in Post-menopausal Women

To describe the impact of coronary artery bypass graft (CABG) surgery on health related quality of life (HRQOL) in post-menopausal women. Prospective cohort study. Women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS). One hundred and thirty-seven women (mean age 66.6) who had CABG surgery while enrolled in HERS. Physical function was assessed using the 12-item Duke Activity Status Index (DASI), energy-fatigue with the four-item RAND scale, and mental health with the RAND mental health inventory each year. We defined baseline HRQOL from the interview that preceded the CABG (mean 4.6 months pre-CABG). To assess post-CABG HRQOL, we used the first interview that was obtained at least 6 months following the CABG (mean 11.5 months post-CABG). For all three measures of HRQOL, mean scores post-CABG were virtually identical to mean scores pre-CABG (mean pre and post scores were 20.8, 20.4 for physical function, 49.3, 49.2 for energy-fatigue, and 71.9 and 72.3 for mental health). After adjusting for demographic and clinical characteristics and the expected temporal change in HRQOL, differences between pre and post-operative HRQOL remained minimal. However, on an individual patient level, there was significant variability in HRQOL outcomes. For example, while mean physical function scores changed little, 32% of women were at least moderately better (scores improved by at least 0.5 standard deviations) following surgery, while 26% were at least moderately worse (scores declined by at least 0.5 standard deviations). Following CABG surgery in post-menopausal women, on average, HRQOL is virtually identical to the pre-operative baseline. However, there is significant variability, as substantial numbers of women are significantly better or significantly worse.

Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor‐positive breast cancer

Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chemotherapy in breast cancer patients. The need for preoperative chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive tumors. This randomized, controlled, phase 2 study evaluated the efficacy of neoadjuvant chemotherapy compared with endocrine treatment with aromatase inhibitors in postmenopausal women with ER-positive and/or PgR-positive breast cancer. Eligible patients were randomly assigned to receive neoadjuvant anastrozole 1 mg/day (n = 61) or exemestane 25 mg/day (n = 60) for 3 months or doxorubicin 60 mg/m(2) with paclitaxel 200 mg/m(2) (four 3-week cycles). Study end points included overall objective response determined by palpation, mammography, and ultrasound, and the number of patients who qualified for breast-conserving surgery and radiotherapy. Clinical objective response was 64% in the endocrine therapy and chemotherapy treatment groups. Median time to clinical response was 57 and 51 days with aromatase inhibitors and chemotherapy, respectively (P > .05). Rates of pathological complete response (3% vs 6%) and disease progression (9% vs 9%) did not differ significantly in the endocrine therapy or chemotherapy group, respectively (P > .05). Rates of breast-conserving surgery were slightly higher in the endocrine group (33% vs 24%; P = .058). The most frequent toxicities from chemotherapy were alopecia (79%), grade 3/4 neutropenia (33%), and grade 2 neuropathy (30%). Endocrine treatment was well tolerated. No deaths occurred during the preoperative treatment. Preoperative neoadjuvant endocrine therapy with aromatase inhibitors was well tolerated and resulted in rates similar to chemotherapy in overall objective response and breast-conserving surgery in postmenopausal women with ER-positive and/or PgR-positive tumors.

Does retention of the ovaries improve long-term survival after hysterectomy? A gynecological oncological perspective

Ovarian cancer is, in most cases, a lethal disease as it is virtually impossible to diagnose at an early stage and almost impossible to treat successfully when detected at an advanced stage. In postmenopausal women, there is no prevention for ovarian cancer but oophorectomy. Therefore, from the gynecological oncological perspective, where benign gynecological pathology requires surgery in postmenopausal women, oophorectomy should be the preferred option.

Neoadjuvant Treatment of Postmenopausal Breast Cancer With Anastrozole, Tamoxifen, or Both in Combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) Multicenter Double-Blind Randomized Trial

The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) trial was designed to test the hypothesis that the clinical and/or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor (ER) -positive, invasive, nonmetastatic breast cancer might predict for outcome in the Arimidex, Tamoxifen Alone or in Combination (ATAC) adjuvant therapy trial. Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or locally advanced potentially operable breast cancer were randomly assigned to neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination of tamoxifen and anastrozole for 3 months. The tumor objective response (OR) was assessed by both caliper and ultrasound. Comparisons were also made of clinical response with ultrasound response, actual and feasible surgery with feasible surgery at baseline, OR in human epidermal growth factor receptor 2 (HER2)-positive cancers, and tolerability. There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen, anastrozole, or the combination. In patients who were assessed as requiring mastectomy at baseline (n = 124), 44% of patients received breast-conserving surgery (BCS) after anastrozole compared with 31% of patients after tamoxifen (P = .23); this difference became significant for patients who were deemed feasible for BCS by their surgeon (46% v 22%, respectively; P = .03). The OR for patients with HER2-positive cancer (n = 34) was 58% for anastrozole compared with 22% for tamoxifen (P = .18). All treatments were well tolerated. Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women, but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled.

Radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery in postmenopausal women with stage I breast cancer: a decision analysis.

To compare outcomes for hypothetical cohorts of postmenopausal patients with estrogen receptor-positive tumors that are < or = 2 cm in size, with pathologically uninvolved axillary nodes, treated with radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery. A Markov model was used to simulate patients' clinical course and estimate overall survival, recurrence-free survival, time with an intact breast, and death from breast cancer. Probabilities were derived from randomized trials and retrospective studies. Analyses were performed separately by age of diagnosis in 5-year increments from 50 to 80 years. Sensitivity analyses tested the stability of radiation benefit. The modeled recurrence-free survival benefit of giving radiation therapy was 3.35 years for women who were 50 years of age at diagnosis, versus 0.61 years for women who were 80 years of age. In the 50-year-old cohort, radiation therapy resulted in additional 0.60 years survival, compared with 0.04 years among 80-year-olds. A 50-year-old woman who received radiation therapy plus tamoxifen was less likely to die from breast cancer than if she received tamoxifen alone (2.43% v 5.29%; relative-risk reduction, 54%). An 80-year-old woman had a 1.17% chance of dying from breast cancer if she received radiation therapy plus tamoxifen, versus 2.02% with tamoxifen alone (relative-risk reduction, 42%). Sensitivity analyses showed that the magnitude of benefit was strongly influenced by including unequal rates of developing distant disease after breast recurrence between the treatment arms and varying rates of local recurrence. The absolute and relative benefits of radiation therapy and individual patient preferences for different health states should be considered when selecting treatment.

Long term oestrogen plus progestin increased venous thromboembolism and biliary tract surgery in postmenopausal women

(2002) JAMA. 288, 58; Hulley S, Furberg C, Barrett-Connor E . , et al., for the HERS Research Group. . Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart...

Long-term estrogen plus progestin increased venous thromboembolism and biliary tract surgery in postmenopausal women

Long-term estrogen plus progestin increased venous thromboembolism and biliary tract surgery in postmenopausal women

Risk of Discovering Endometrial Carcinoma or Atypical Hyperplasia during Hysteroscopic Surgery in Postmenopausal Women

Study ObjectiveTo assess the risk of diagnosing endometrial carcinoma or atypical hyperplasia in tissue resected during hysteroscopy performed for intrauterine pathology presumed benign in postmenopausal women. DesignA single-center prospective study (Canadian Task Force classification II-2). SettingDepartment of Gynecology, La Conception Hospital, Marseille, France. PatientsThree hundred twenty-five women with intrauterine pathology, presumed benign, causing postmenopausal bleeding or bleeding related to hormone replacement therapy. InterventionAll women had an endometrial biopsy after diagnostic hysteroscopy to exclude endometrial carcinoma or atypical hyperplasia. Then they underwent hysteroscopic surgical resection (203, 62.5%) or endometrial ablation (122, 37.5%). Measurements and Main ResultsTwo cases each (0.6%) of endometrial carcinoma and endometrial atypical hyperplasia were discovered that were missed by preoperative evaluations. ConclusionOutpatient hysteroscopy and endometrial biopsy do not eliminate the finding of carcinoma or endometrial atypical hyperplasia, as these disorders may be discovered during hysteroscopic surgery.

Hormone replacement therapy in postmenopausal women with heart disease and risk for gallstones that require surgery.

Summaries for Patients2 October 2001Hormone Replacement Therapy in Postmenopausal Women with Heart Disease and Risk for Gallstones That Require SurgerySearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-7-200110020-00004 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail What is the problem and what is known about it so far?Two types of hormones, estrogens and progestins, are useful in treating the symptoms of menopause. These hormones may prevent some of the unwanted health problems in postmenopausal women, such as thinning of the bones (osteoporosis). It is unclear whether these hormones also prevent other undesired health problems, such as heart disease, colon cancer, and Alzheimer disease. Estrogens and progestins also have side effects. For example, estrogen increases the risk for gallstones. Gallstones are hard deposits (“stones”) that form in the gallbladder, a small organ that makes substances that ... Author, Article, and Disclosure InformationAffiliations: The summary below is from the full report titled “Effect of Estrogen plus Progestin on Risk for Biliary Tract Surgery in Postmenopausal Women with Coronary Artery Disease. The Heart and Estrogen/progestin Replacement Study.” It is in the 2 October 2001 issue of Annals of Internal Medicine (volume 135, pages 493-501). The authors are JA Simon, DB Hunninghake, SK Agarwal, F Lin, JA Cauley, CC Ireland, and JH Pickar, for the Heart and Estrogen/progestin Replacement Study (HERS) Research Group.Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine.Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians-American Society of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffect of Estrogen plus Progestin on Risk for Biliary Tract Surgery in Postmenopausal Women with Coronary Artery Disease: The Heart and Estrogen/progestin Replacement Study Joel A. Simon , Donald B. Hunninghake , Sanjay K. Agarwal , Feng Lin , Jane A. Cauley , Christine C. Ireland , James H. Pickar , and Metrics 2 October 2001Volume 135, Issue 7Page: I-44KeywordsCardiac surgeryCardiovascular therapyEstrogen replacement therapyEstrogensGallbladderHeartHormonesHypercholesterolemiaLongitudinal studiesSurgery ePublished: 2 October 2001 Issue Published: 2 October 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Eliciting patients' preferences for adjuvant chemotherapy in breast cancer: development and validation of a bedside decision-making instrument in a French Regional Cancer Centre.

In developed countries, the physician-patient relationship is moving from a paternalistic model to new decision-making models that take patient preferences into account. OBJECTIVES: Our aim was to develop a Decision Board (DB) and to test its acceptability in a French Regional Cancer Centre regarding the decision on whether or not to use chemotherapy after surgery in postmenopausal women with breast cancer. This paper presents the development process for this instrument and reports the pretesting phase, as well as the corresponding results. METHODS: A working group was created with oncologists, psychologists and economists. Following the first phase, i.e. the development process, a first version of the instrument was presented to health professionals. Their feedback led to important modifications of the instrument. The DB was then presented to experienced patients, which resulted in slight changes. The second phase consisted of pretesting the comprehension, internal and across-time consistency of the DB on healthy volunteers. RESULTS: The DB was pretested in a group of 40 healthy volunteers. Eighteen respondents chose chemotherapy and 22 chose not to have chemotherapy. Comprehension rates were very high (>/=87.5%). Internal consistency was assessed considering option attitudes based on outcomes and option attitudes based on process. Women shifted their choices in a predictable way. Across-time consistency was appraised using the test-retest method with Visual Analog Scales. The Intraclass Correlation Coefficient was 0.97. DISCUSSION-CONCLUSION: Due to cultural differences, the DB developed in our French Cancer Centre is quite different from the DBs previously developed elsewhere. Our instrument showed good comprehension and consistency properties, which are corroborated by the DB literature. Whether our DB is acceptable for patients with breast cancer must still be tested. Patients' reactions will tell us which type of decision-making model is at work. Further research is needed in order to explore the shared decision-making process and clarify the concept.

Urinary steroids at time of surgery in postmenopausal women with breast cancer.

Urinary steroid metabolites were measured by capillary gas chromatography in 22 postmenopausal women with operable breast cancer on day before the tumour excision and in 20 hospitalised control who were before an operation from other cause than cancer. Serum dehydroepiandrosterone-sulphat (DHEAS) and testosterone (T) level were measured by radioimmunassay in the same groups and same time. There was no significant difference in the level of urinary androgen metabolites. Pregnanediol level was significantly lower (P < 0.05) in cancer patients. In the 5 patients with positive axillary nodes the tetrahydrocortisol and alpha-cortolone levels were significantly (P < 0.05) higher than in node negative ones. There was no significant differences in the serum DHEAS and T levels. These results indicate that metabolic changes are existing in postmenopausal patients which may be a cause or a consequence of the disease.

Hysteroscopic surgery in postmenopausal women.

To assess the efficacy of hysteroscopic surgery in postmenopausal women presenting with abnormal uterine bleeding. A retrospective audit of 102 patients. The Department of Obstetrics and Gynecology B, La Conception Hospital, Marseilles, France. One hundred and two women between the ages of 47-67 years with postmenopausal bleeding or bleeding related to hormone replacement therapy were evaluated by pelvic ultrasound and diagnostic hysteroscopy. A benign organic cause was noted in 87 cases (polyps in 51 and fibroids in 36.) Fifteen patients had no significant disease. Resection of polyps or fibroids, endometrial ablation. One hundred and seven procedures were performed on 102 patients. Major operative complications were rare and included one perforation and one case of glycine toxicity. Eighty-eight patients were satisfied with the results. Six patients were subsequently treated by hysterectomy. Six patients complained of recurrent abnormal bleeding. This modality of treatment appears to be effective over the long term. The operative criteria should take the causes of bleeding and not just the age of the patient into account.

Surgery in postmenopausal women ? the value of transvaginal sonography

Transvaginal sonography is a recent addition to the diagnostic techniques available for the evaluation of the female pelvis. Transvaginal sonography is performed with a high-frequency transducer placed in the vagina where it is in close anatomic proximity to the pelvic structures. The procedure overcomes difficulties in imaging obese patients, those with a large amount of bowel gas, and those with inadequate bladder filling. Our experience in over 200 cases of postmenopausal women is the subject of this review. This technique has been employed to detect ovarian and adnexal abnormalities, endometrial changes (hyperplasia and endometrial carcinoma), myometrial invasion, fibroids, adnexal torsion and free fluid in the rectouterine fossa. The results suggest that transvaginal sonography has considerable advantages in the evaluation of pelvic structures in postmenopausal women prior to planned surgical exploration.