Hormone Replacement Therapy in Breast Cancer Survivors

Abstract: The use of hormone replacement therapy (HRT) in postmenopausal breast cancer survivors is controversial. This report describes the symptomatic benefit of HRT and the subsequent risk of recurrent breast cancer in a group of postmenopausal women with a prior history of locally treated breast cancer. One-hundred and fourteen disease-free patients received HRT to control estrogen deficiency problems after local breast cancer therapy. Thirty-three had American Joint Committee on Cancer (AJCC) stage O at diagnosis, 43 stage 1, 24 stage 2A, 12 stage 2B, 1 stage 3A, and 1 stage 3B. Pathology was infiltrating carcinoma in 81, ductal carcinoma in situ (DCIS) 29, and lobular carcinoma in situ 4. Fifty-six were receiving HRT at the time of breast cancer diagnosis with 20 continuing HRT. One-hundred and eight patients received either an estrogen or an estrogen/progestin combination with 6 receiving vaginal estrogens. The time from breast cancer diagnosis to initiation of HRT ranged from .0 to 23.9, mean 3.7 years. HRT was administered for hot flashes in 77%, dyspareunia/vaginal dryness 53.5%, reactive depression/anxiety 34%. The duration of replacement therapy ranged from .10–17.5, mean 2.5 years. Hot flashes were relieved in 98%, dyspareunia/vaginal dryness 95%, and reactive depression/anxiety 95%. One new primary or ipsilateral breast recurrence (DCIS with microinvasion) 1.8%, (1/56, 95% confidence interval [Cl], .045–9.6%) was observed. One patient developed DCIS within breast tissue left on the chest wall after a modified mastectomy. Two new contralateral primaries, 2.0%, (2/103, 95% Cl, .24-6.8%) were observed. One occurred in the contralateral breast during therapy for an ipsilateral chest wall and systemic recurrence. Three patients, 3.0% (3/114, 95% Cl, .55–7.5%) have experienced systemic relapse with two deaths. In this selected group of postmenopausal women survivors, HRT dramatically relieved estrogen deficiency symptoms and did not appear to increase the risk of an ipsilateral, contralateral, or systemic recurrence.     

Bone-Resorbing Cytokines from Peripheral Blood Mononuclear Cells after Hormone Replacement Therapy: A Longitudinal Study

Conflicting results have been reported in several cross-sectional studies measuring cytokine production from adherent monocytes in pre- and postmenopausal women. Furthermore, the target cells for the action of estrogen are still debated. We therefore assessed in a longitudinal manner the cytokine production from different fractions of peripheral blood mononuclear cells (PBMC) cultured for 48 h. PBMC were obtained from 30 postmenopausal women before and after 6 months of hormone replacement therapy (HRT). Women were randomly allocated to two groups: an adherent PBMC group (n= 20) and a total PBMC group (n= 9). After 6 months of treatment, urinary pyridinoline levels were markedly decreased in both groups (353 ± 24 vs 114 ± 13 μg/mmol creatinine and 325 ± 35 vs 164 ± 31 μg/mmol creatinine respectively, p<0.01). Culture supernatants were assayed for interleukin 1β (IL-1β), interleukin 6 (IL-6), soluble IL-6 receptor (IL-6rs) and tumor necrosis factor alpha (TNF-α). In the adherent PBMC group, HRT induced a nonsignificant trend toward decreased levels of IL-1β (35 ± 10 vs 13 ± 5 pg/ml), TNF-α (333 ± 58 vs 222 ± 30 pg/ml) and IL-6 (115 ± 70 vs 17 ± 10 pg/ml). In contrast, in the total PBMC group, HRT induced a consistent and dramatic decrease in levels of IL-1β (104 ± 22 vs 25 ± 8 pg/ml), IL-6 (5950 ± 1041 vs 1011 ± 361 pg/ml), IL-6rs (148 ± 33 vs 35 ± 12 pg/ml) (p<0.01) and TNF-α (1468 ± 315 vs 585 ± 207 pg/ml, p= 0.05). We then evaluated whether HRT had the same effect in vitro. Adherent or total PBMC of 8 postmenopausal women were cultured with or without 10⁻⁸M 17β-estradiol or tibolone for 48 h. Production of IL-1β, TNF-α, IL-6 and IL-6rs was not affected by the presence of 17β-estradiol or tibolone in cultures of these cell fractions. In conclusion, our data indicate that non-adherent PBMC could mediate the response to HRT. HRT may exert its action indirectly via noncirculating cells, as suggested by the absence of an in vitro effect. Received: 11 July 2000 / Accepted: 15 January 2001     

Educational Review Hormone Replacement Therapy and Breast Cancer

The use of hormone replacement therapy by postmenopausal women with a history of breast cancer is a subject of considerable controversy. There are no scientific studies that have appropriately examined the issue, and current practice is often based on inferences from indirect evidence, anecdotal experience, and personal bias. Our understanding of the effects of exogenous, as well as endogenous, hormones on normal and neoplastic breast tissue provides some insights but is not an appropriate basis for clinical practice. The effects of exogenous hormone replacement on the overall health of postmenopausal women, including psychosocial issues, cardiovascular risks, and the morbidity of osteoporosis, must be understood before patients can be counseled appropriately. Treatment of patients must be individualized. The rapidly expanding area of nonhormonal therapies for the treatment of postmenopausal health risks and the treatment of symptomatic complaints in postmenopausal women has already led to a reevaluation of the use of exogenous hormones among all women. A prospective randomized trial that examines the effects of hormone replacement on women with a history of breast cancer is currently underway and will provide valuable data to address these issues. The aim of this review is to outline the scientific basis for the association between estrogen and breast cancer and to provide a framework in which individualized recommendations concerning the use of hormone replacement therapy can be made for patients with breast cancer.     

Total Hip Replacement in Sickle Cell Disease Patients with Avascular Necrosis of Head of Femur: A Retrospective Observational Study

BackgroundFemoral head avascular necrosis leads to osteoarthritis of the hip joint and affects its functional capacity in sickle cell disease patients. The functional outcomes of total hip replacement (THR) on patients with congruous joints who underwent hip replacement after having a failed joint preservation surgery are unknown. This study aimed to compare the functional outcomes of THR in patients with sickle cell disease having avascular necrosis with and without loss of hip joint congruency.MethodsThis retrospective study included 35 patients (age, 20–52 years; 18 males and 17 females) who underwent uncemented THR. Patients were divided into Group-A (n = 18, good hip joint congruency) and Group-B (n = 17, obliterated hip joint congruency). The Harris Hip Score (HHS) was used to assess functional outcomes. All patients were followed up at 6-weekly intervals then 6-monthly intervals.ResultsThe mean follow-up period was 8.26 ± 3.01 years. The mean preoperative HHSs of Group-A and Group-B were 45.22 ± 3.021 and 25.94 ± 4.437, respectively. Postoperatively, a subsequent increase in HHS was found in both groups, and a significant difference between the groups was observed at 6 weeks (p < 0.0001*) and 1 year (p < 0.0006*). Interestingly, HHS was not significantly different (p = 0.0688) at 5-year follow-up between the groups. The differences in HHS within the group at each subsequent follow-up were also statistically significant (ANOVA, p < 0.0001*).ConclusionA significant improvement was observed with THR in both groups. Nevertheless, the flattened hip joint congruency group showed significantly better HHS improvements than the normal congruency groups. These findings may aid in the decision-making capabilities of the surgeons.     

Strategy for Selective Middle Hepatic Vein Reconstruction in Living Donor Liver Transplantation Using Right Lobe Graft: A Retrospective Observational Study

BackgroundThe aim of this study was to verify the safety and feasibility of our selection criteria for middle hepatic vein (MHV) reconstruction in living donor liver transplantation (LDLT) using right lobe grafts.MethodsA total of 153 LDLTs were performed using right lobe grafts in a tertiary hospital from 2006 to 2016. Among them, 52 cases without MHV reconstruction were compared with 101 recipients who underwent LDLT using right lobe graft with MHV reconstruction. Both groups were compared regarding indications for reconstruction, short-term and long-term complications, operative details, and outcomes.ResultsThe two groups differed only in cold ischemic time (108.19 ± 49.81 minutes vs 146.37 ± 58.74 minutes) preoperatively. Short-term posttransplant outcomes, long-term overall survival, and long-term disease-free survival showed no significant differences between the 2 groups. After propensity score matching for both groups with and without MHV reconstruction to eliminate selection bias, the 2 groups were comparable.ConclusionsWe found that our selection criteria for performing MHV reconstruction in LDLT using right lobe graft were feasible and safe. A routine MHV reconstruction is not necessary if the right lobe graft graft-to-recipient weight ratio is ≥1.0, right hepatic vein draining territory volume is ≥0.8, and recipient Model for End-Stage Liver Disease score is <20.     

One-Year Outcome After Cardiac Surgery for Patients With Cancer: An Observational Monocentric Retrospective Study

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Total Hip Replacement Influences Spinopelvic Mobility: A Prospective Observational Study

BackgroundAbnormal spinopelvic mobility is identified as a contributing element of total hip arthroplasty (THA) instability. Preoperative identification of THA patients at risk is still a remaining challenge. We therefore conducted this study to (1) evaluate if preoperative and postoperative spinopelvic mobility differs, (2) determine the interactions between the elements of the spinopelvic complex, and (3) identify preoperative parameters for predicting spinopelvic mobility.MethodsA prospective observational study assessing 197 THA patients was conducted with biplanar stereoradiography in standing and relaxed sitting positions preoperatively and postoperatively. Two independent investigators determined spinopelvic mobility based on 2 different classifications (Δ sacral slope [SS] and Δ pelvic tilt [PT]; Δ from standing to sitting; Δ < 10° stiff, Δ ≥ 10°-30° normal, Δ > 30° hypermobile). Multiple regression analysis and receiver operating characteristic analysis were used to identify predictors for postoperative spinopelvic mobility.ResultsSpinopelvic mobility significantly increased after THA based on ΔPT (Pre/Post: 18.5°/22.8°; P < .000) and ΔSS (Pre/Post 17.9°/22.4°; P < .000). A distinct shift in the ratio from stiff (Pre/Post: 24%/9.7%) to hypermobile (Pre/Post: 10.2%/22.1%) mobility postoperatively was observed. Receiver operating characteristic analysis predicted postoperative stiffness using preoperative PT_Standing ≥ 13.0° with a sensitivity of 90% and a specificity of 51% and hypermobility with preoperative SS_Standing ≥ 35.2° with a sensitivity of 81% and a specificity of 34%. Age at surgery, preoperative PT_Standing, and pelvic incidence were independent predictors of spinopelvic mobility (R² = 0.24).ConclusionDefinition of preoperative stiffness should be interpreted with caution by arthroplasty surgeons as mobility itself is influenced by THA. For the first time thresholds for standing preoperative parameters for predicting postoperative spinopelvic mobility could be provided. For preoperative standing only lateral assessment could serve as a screening tool for spinopelvic mobility.     

Mammographic Density in Women on Postmenopausal Hormone Replacement Therapy

Background . Fine-needle aspiration (FNA) biopsy has been used increasingly in the diagnosis and biologic characterization of breast carcinomas in patients who receive preoperative chemotherapy. Because proliferative activity of breast carcinoma has been shown to be of prognostic significance, the authors compared immunocytochemical Ki-67 growth fraction and flow cytometric S-phase fraction (SPF), both evaluated on FNA samples. Methods . The proliferative activity of 134 FNA samples from primary breast carcinoma patients was studied using both immunocytochemistry with the monoclonal antibody Ki-67 and SPF determined by DNA flow cytometry. Results . Ki-67 and SPF were evaluable in 114 and 107 cases, respectively, and both were evaluable in 95 cases. Of the 134 FNA samples studied, 37% were diploid and 63% were aneuploid. The distribution of both Ki-67 and SPF was different in diploid and aneuploid tumors. The median Ki-67 value as well as the median SPF were significantly higher in aneuploid versus diploid tumors (p < 0.001). Median Ki-67 and SPF values were used to discriminate between low versus high proliferating tumors. The overall concordance between Ki-67 and SPF was 75% (p < 0.001). A good correlation was found between Ki-67 and SPF (correlation coefficient = 0.72; p < 0.001). Conclusions . The results of the current study suggest the Ki-67 growth fraction and SPF determined by FNA may be used as measurements of the proliferative activity of breast carcinoma. The authors recommend these determinations be used as preoperative procedures in patients with a cytologic diagnosis of breast carcinoma who are candidates for neoadjuvant chemotherapy and/or endocrine therapy.     

Influence of Current and Past Hormone Replacement Therapy on Bone Mineral Density: A Study of Discordant Postmenopausal Twins

There is controversy about the ideal timing of hormone replacement therapy (HRT) and duration of treatment. In this study we have examined intrapair differences in bone mineral density (BMD) in twins who were discordant for HRT use. Twin pairs in which only one co-twin had been exposed to HRT for more than 12 months continuously were selected from 365 postmenopausal monozygotic (MZ) and dizygotic (DZ) pairs recruited as part of the St Thomas’ Adult UK Twin Registry of normal volunteers. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. Intrapair differences in BMD between HRT users and non-users were compared. A total of 65 HRT-discordant pairs were identified, of which 36 were discordant for current HRT use (mean age: 55.3 years, median duration of HRT use: 36 months) and 29 were discordant for past HRT use (mean age: 60.4 years, median HRT duration: 30 months). Among current users BMD was consistently and significantly higher than in non-users at both sites (lumbar spine mean intrapair difference (IPD%): 12.3%, 95% confidence interval (CI): 7.1%, 17.5%; femoral neck IPD%: 8.6%, 95% CI: 3.4%, 13.7%). The intrapair differences were substantially smaller when past users and non-users were compared (lumbar spine IPD%: 2.4%, 95% CI: −3.7%, 8.6%; femoral neck IPD%: 0.4%, 95% CI: −5.3%, 6.0%). These differences remained little changed after adjusting for the potential confounding effects of the duration of HRT use, and intrapair differences in alcohol and tobacco consumption and physical exercise. The results confirm, in a closely matched design, the findings of other observational research that current use of HRT has a major effect on BMD at the lumbar spine and femoral neck. Past users of HRT do not, however, show the same benefits. The clinical implications of these findings are that HRT needs to be used continuously to influence BMD and that alternative treatments need to be considered in those who discontinue HRT. Received: 18 August 1997 / Accepted: 4 June 1998     

Mismatch Repair Proteins in Oropharyngeal Squamous Cell Carcinoma: A Retrospective Observational Study

Cases of oropharyngeal squamous cell carcinoma are on the rise and the disease now ranks as the most common human papillomavirus-related cancer. Although risk factors have been extensively discussed in the literature, the role of the DNA mismatch repair system remains unanswered. To evaluate the impact of the DNA mismatch repair (MMR) protein immunostaining on the tumor progression and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). This retrospective observational study comprised 50 cases of OPSCC. Immunohistochemistry for MSH2, MSH6, PMS2, MLH1, Ki67, p16 and caspase-3 was performed. The expression of these proteins was assessed in surgical resection margins, primary tumor (PT), and lymph node metastasis (LNM) of p16+ and p16- OPSCC. Clinical-pathological involvement in immunostaining was evaluated with Kruskal–Wallis/Dunn or Mann–Whitney test, Wilcoxon test and Spearman’s correlation. Overall survival (OS) was analyzed with Log-Rank Mantel-Cox and Cox regression. MSH6 and caspase-3 showed high expression in PT (p16+ and p16 −) and in LNM (p16+ and p16−), and high levels of MSH2 were found in LNM (p16+ and p16 −). An imbalance in MutSα also was observed. PMS2 and caspase-3 expression was associated with poor survival in p16- OPSCC and, in multivariate analysis, MSH2, MSH6 and MLH1 had the poorest prognostic impact in p16+ OPSCC. MMR protein immunostaining is involved in OPSCC progression, dissemination and prognosis. The overexpression of MMR proteins as a response to increased DNA mismatch caused by cell proliferation and MSH2, MSH6 and MLH1 proteins might constitute a prognostic marker in p16+ OPSCC.     

Intrafamilial Transmission of Rosacea Spanning Six Generations: A Retrospective Observational Study

Rosacea hereditary predisposition has been hypothesized based on family inheritance and twin concordance. Currently, information concerning intrafamilial rosacea transmission are still limited to few generations. The aim of our study was to assess data on rosacea intrafamilial transmission spanning six generations. One-hundred and thirty patients affected by rosacea who visited our acne and rosacea clinic from June 2018 to June 2019 were consecutively enrolled in this study. During clinical evaluation, an accurate anamnesis, including familiarity across six generations, which included vertical, horizontal, and combined transmission, was performed. Affected relatives were clinically evaluated, and in those in which clinical consultation was not feasible, clinical photos were obtained. The results showed that 64 of 130 patients (49.2%) were positive for at least a family member with rosacea. In addition, 90 affected relatives (69.2%) were identified by extending the familial investigation to the whole kindred, finding a percentage of familiarity (69.2%) higher than that reported in the literature (30-50%) with a 1:1.4. ratio of patients positive for familiarity/affected relative. Our study contributes to add knowledge about intrafamilial involvement in rosacea. Extending the search to all potential affected parents and offspring of rosacea patients can promote early diagnosis along with the adoption of correct therapeutic interventions and educational programs to prevent the exposure to triggering or exacerbating factors.     

Attitudes to Osteoporosis and Hormone Replacement Therapy among Elderly Women

This study compares the attitudes toward osteoporosis and its treatment between a group of elderly women admitted to hospital for therapy of an osteoporotic fracture and a control group admitted for joint replacement surgery. We surveyed 97 women (64 with a fracture, and 33 controls) and found that the two groups of patients demonstrated a similar risk factor profile for osteoporosis and poor knowledge of osteoporosis and its available treatments, including hormone replacement therapy (HRT). By selecting a control group of women with no recent fracture, we hoped to highlight the effect of sustaining a recent fracture on attitudes to treatment. Initially only 10% (8 in the fracture group and 2 in the control group) were interested in treatment for osteoporosis, but those women who had been admitted with a fracture were significantly more receptive to education about osteoporosis and to the offer of further investigation and treatment of osteoporosis (38 versus 10, p= 0.007). We conclude that it is worthwhile offering education, screening and treatment to elderly patients who present with a fracture. Received: 11 June 1997 / Accepted: 6 April 1998     

Parathyroid Hormone and T-Cellular Immunity in Uremic Patients in Replacement Dialytic Therapy

Abstract: We studied 54 patients in replacement dialytic therapy divided into two groups: Group 1, 26 patients with normal parathyroid hormone (PTH) (10–80 pg/ml); and Group 2, 28 patients with elevated PTH (80–400 pg/ml). Total T lymphocytes, CD4, CD8, and CD4/CD8 ratio were evaluated. We found a reduction of total T lymphocytes in both groups compared with controls. A decrease of CD4 and CD4/CD8 ratio with a rise of CD8 occurred in Group 2 but not in Group 1. In Group 2, PTH presented a linear correlation with CD8 and a reverse correlation with total T cells, CD4, and CD4/CD8 ratio. PTH might act on T-cellular immunity with an immunosuppressive effect from the earlier phases of hyperparathyroidism.