Information needs of post-menopausal women with hormone receptor positive early-stage breast cancer considering adjuvant endocrine therapy

Objective

To identify questions that post-menopausal women with receptor-positive early-stage breast cancer want answered before their adjuvant-endocrine-therapy decision is made.

Methods

We surveyed patients eligible for adjuvant-endocrine therapy in the previous 3–18 months. Participants rated the importance of getting each of 95 questions answered before the decision is made (options: essential/desired/not important or no opinion/avoid). For each question rated “essential”/“desired”, the participant also identified the purpose(s) for the answer: to help her understand, decide, plan, or other reason(s).

Results

The response rate was 55% (188/343). Participants rated a mean of 57 (range: 1–95) questions “essential”, 80 (range: 1–95) “essential” or “desired”, and 2 (range: 0–27) “avoid”. Every question was “essential” to ≥31% of participants, and “essential”/“desired” to ≥63%. All but eleven questions were rated as “avoid” by ≥1 participant. The most frequent purposes for “essential” questions were to: understand their situations (mean 45, range: 0–95), decide (mean 18, range: 0–94), and plan (mean 13, range: 0–95).

Conclusion

Many patients want a lot of information before this decision is made but there is wide variation within the group in both the number and in which questions they want answered.

Practice implications

Patient education in this setting needs to be tailored to the needs of the individual patient.     

Use of alternative medicine by women with early-stage breast cancer.

BACKGROUND: We analyzed the use of alternative medicine by women who had received standard therapy for early-stage breast cancer diagnosed between September 1993 and September 1995. METHODS: A cohort of 480 patients with newly diagnosed early-stage breast cancer was recruited from a Massachusetts statewide cohort of women participating in a study of how women choose treatment for cancer. Alternative medical treatments, conventional therapies, and health-related quality of life were examined. RESULTS: New use of alternative medicine after surgery for breast cancer was common (reported by 28.1 percent of the women); such use was not associated with choices about standard medical therapies after we controlled for clinical and sociodemographic variables. A total of 10.6 percent of the women had used alternative medicine before they were given a diagnosis of breast cancer. Women who initiated the use of alternative medicine after surgery reported a worse quality of life than women who never used alternative medicine. Mental health scores were similar at base line among women who decided to use alternative medicine and those who did not, but three months after surgery the use of alternative medicine was independently associated with depression, fear of recurrence of cancer, lower scores for mental health and sexual satisfaction, and more physical symptoms as well as symptoms of greater intensity. All groups of women reported improving quality of life one year after surgery. CONCLUSIONS: Among women with newly diagnosed early-stage breast cancer who had been treated with standard therapies, new use of alternative medicine was a marker of greater psychosocial distress and worse quality of life.     

Effects of stress management on testosterone levels in women with early-stage breast cancer

We examined the effects of a10-week, group-based cognitive-behavioral stressman-agement (CBSM) intervention on serum testosterone levels in women with Stage 1or 2 breast cancer. At 4 to 8 weeks postsurgery, participants were randomized to CBSM (n = 24) or to a wait-list control group (n = 10). Free and total testosterone was assessed via radioimmunoassay before and after the study period. The participants also completed a questionnaire assessing the degree to which living with breast cancer had led to social and emotional benefits in their life. We observed significant decreases in testosterone levels in the CBSM group and no change in the controls. Decreasesintes-tosterone were related to increases in positive contributions. These findings suggest that a short-term psychological intervention can help modulate androgen functioning, and these changes are related to enhanced benefit finding observed among women with breast cancer participating in CBSM.     

Pathology parameters and adjuvant tamoxifen response in a randomised premenopausal breast cancer trial

BACKGROUND: Subgroups of breast cancer that have an impaired response to endocrine treatment, despite hormone receptor positivity, are still poorly defined. Breast cancer can be subdivided according to standard pathological parameters including histological type, grade, and assessment of proliferation. These parameters are the net result of combinations of genetic alterations effecting tumour behaviour and could potentially reflect subtypes that respond differently to endocrine treatment. AIMS: To investigate the usefulness of these parameters as predictors of the response to tamoxifen in premenopausal women with breast cancer. MATERIALS/METHODS: Clinically established pathological parameters were assessed and related to the tamoxifen response in 500 available tumour specimens from 564 premenopausal patients with breast cancer randomised to either two years of tamoxifen or no treatment with 14 years of follow up. Proliferation was further evaluated by immunohistochemical Ki-67 expression. RESULTS: Oestrogen receptor positive ductal carcinomas responded as expected to tamoxifen, whereas the difference in recurrence free survival between control and tamoxifen treated patients was less apparent in the relatively few lobular carcinomas. For histological grade, there was no obvious difference in treatment response between the groups. The relation between proliferation and tamoxifen response seemed to be more complex, with a clear response in tumours with high and low proliferation, whereas tumours with intermediate proliferation defined by Ki-67 responded more poorly. CONCLUSIONS: Clinically established pathology parameters seem to mirror the endocrine treatment response and could potentially be valuable in future treatment decisions for patients with breast cancer.     

Behaviour of metastasis in relation to vascular index in patients with node-positive breast cancer treated with adjuvant tamoxifen

Some experimental studies suggested that one possible oestrogen-receptor-unrelated mechanism of action of tamoxifen involves inhibition of angiogenesis. We evaluated the correlation of the degree of vascularisation of the primary tumour and we assessed it by using the panendothelial marker anti- CD31 and immunohistochemistry with microvessels count, performed at the vascular ‘hot spot’ of each single cancer, with the risk of recurrence in time. A cohort of 176 consecutive patients with node-positive invasive breast cancer treated with adjuvant tamoxifen (30 mg/daily for 3 years) and a median follow-up of 72 months was studied. Sixty-two patients developed metastasis (30 visceral, 18 skeletal and 14 in soft tissues) during the time of observation. The study of the hazard function for metastasis was performed by a generalized linear modelling approach with a binomial error according to Efron. The risk of first recurrence was strictly associated with vascular index, having the patients with the highest microvessel counts the highest risk of metastasis during all the period of observation. We did not find an interaction of vascularity with oestrogen receptor (ER) status. However, in the subgroup of patients with ER-positive tumours the hazard of metastasis was almost constant in time, while in that with ER-negative tumours it increased rapidly up to 20 months and, thereafter, decreased sharply. The results of our study are an indirect evidence that the patients with highly vascularized breast cancers may gain poor benefit of adjuvant tamoxifen and, therefore, that this antioestrogen is unlikely to retain a clinically relevant antiangiogenic activity in human breast cancer. Our data need confirmation by a prospective randomized clinical trial.     

Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer.

BACKGROUND AND METHODS. Tamoxifen, a synthetic antiestrogen, increases disease-free and overall survival when used as adjuvant therapy for primary breast cancer. Because it is given for long periods, it is important to know whether tamoxifen affects the skeleton, particularly since it is used extensively in postmenopausal women who are at risk for osteoporosis. Using photon absorptiometry, we studied the effects of tamoxifen on the bone mineral density of the lumbar spine and radius and on biochemical measures of bone metabolism in 140 postmenopausal women with axillary-node-negative breast cancer, in a two-year randomized, double-blind, placebo-controlled trial. RESULTS. In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 0.61 percent per year, whereas in those given placebo it decreased by 1.00 percent per year (P less than 0.001). Radial bone mineral density decreased to the same extent in both groups. In a subgroup randomly selected from each group, serum osteocalcin and alkaline phosphatase concentrations decreased significantly in women given tamoxifen (P less than 0.001 for each variable), whereas serum parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not change significantly in either group. CONCLUSIONS. In postmenopausal women, treatment with tamoxifen is associated with preservation of the bone mineral density of the lumbar spine. Whether this favorable effect on bone mineral density is accompanied by a decrease in the risk of fractures remains to be determined.     

不同治疗方法对绝经后乳腺癌患者骨密度的影响

目的 探讨不同治疗方法 对绝经后乳腺癌患者骨密度(BMD)的影响.方法 研究分为健康对照组(50例)、肿瘤组[48例,其中24例再行他莫昔芬(TAM)组治疗].采用双能X线骨密度仪(DEXA)测定所有研究对象的基线BMD.肿瘤组术后均进行辅助化疗,其中24例(TAM组)化疗后继续使用TAM行内分泌治疗.用DEXA测量腰椎和左髋部位的BMD,比较肿瘤组化疗前、后以及TAM组行内分泌治疗8个月后BMD变化.结果 肿瘤组化疗后腰椎部位BMD(0.87±0.15)g/cm2比化疗前(0.93±0.15)g/cm2明显降低(P<0.05);TAM组行内分泌治疗8个月后腰椎BMD(0.90±0.04)g/cm2和股骨颈(0.74±0.05)g/cm2等左髋部位的BMD均有明显增加(P<0.05).结论 化疗可能导致绝经后乳腺癌患者BMD的下降,而TAM治疗能缓解化疗引起的BMD降低.     

Reduced breast cancer incidence in women treated with subcutaneous testosterone,or testosterone with anastrozole: A prospective,observational study

Objectives

There is evidence that androgens are breast protective and that testosterone therapy treats many symptoms of hormone deficiency in both pre and postmenopausal patients. However, unlike estrogen and progestins, there is a paucity of data regarding the incidence of breast cancer in women treated with testosterone therapy. This study was designed to investigate the incidence of breast cancer in women treated with subcutaneous testosterone therapy in the absence of systemic estrogen therapy.

Study design

This is a 5-year interim analysis of a 10-year, prospective, observational, IRB approved study investigating the incidence of breast cancer in women presenting with symptoms of hormone deficiency treated with subcutaneous testosterone (T) implants or, T combined with the aromatase inhibitor anastrozole (A), i.e., T + A implants. Breast cancer incidence was compared with that of historical controls reported in the literature, age specific Surveillance Epidemiology and End Results (SEER) incidence rates, and a representative, similar age group of our patients used as a ‘control’ group. The effect of adherence to T therapy was also evaluated.

Results

Since March 2008, 1268 pre and post menopausal women have been enrolled in the study and eligible for analysis. As of March 2013, there have been 8 cases of invasive breast cancer diagnosed in 5642 person-years of follow up for an incidence of 142 cases per 100 000 person-years, substantially less than the age-specific SEER incidence rates (293/100 000), placebo arm of Women's Health Initiative Study (300/100 000), never users of hormone therapy from the Million Women Study (325/100 000) and our control group (390/100 000). Unlike adherence to estrogen therapy, adherence to T therapy further decreased the incidence of breast cancer (73/100 000).

Conclusion

T and/or T + A, delivered subcutaneously as a pellet implant, reduced the incidence of breast cancer in pre and postmenopausal women. Evidence supports that breast cancer is preventable by maintaining a T to estrogen ratio in favor of T and, in particular, by the use of continuous T or, when indicated, T + A. This hormone therapy should be further investigated for the prevention and treatment of breast cancer.     

Reduced breast cancer incidence in women treated with subcutaneous testosterone,or testosterone with anastrozole: A prospective,observational study

ObjectivesThere is evidence that androgens are breast protective and that testosterone therapy treats many symptoms of hormone deficiency in both pre and postmenopausal patients. However, unlike estrogen and progestins, there is a paucity of data regarding the incidence of breast cancer in women treated with testosterone therapy. This study was designed to investigate the incidence of breast cancer in women treated with subcutaneous testosterone therapy in the absence of systemic estrogen therapy.Study designThis is a 5-year interim analysis of a 10-year, prospective, observational, IRB approved study investigating the incidence of breast cancer in women presenting with symptoms of hormone deficiency treated with subcutaneous testosterone (T) implants or, T combined with the aromatase inhibitor anastrozole (A), i.e., T + A implants. Breast cancer incidence was compared with that of historical controls reported in the literature, age specific Surveillance Epidemiology and End Results (SEER) incidence rates, and a representative, similar age group of our patients used as a ‘control’ group. The effect of adherence to T therapy was also evaluated.ResultsSince March 2008, 1268 pre and post menopausal women have been enrolled in the study and eligible for analysis. As of March 2013, there have been 8 cases of invasive breast cancer diagnosed in 5642 person-years of follow up for an incidence of 142 cases per 100 000 person-years, substantially less than the age-specific SEER incidence rates (293/100 000), placebo arm of Women's Health Initiative Study (300/100 000), never users of hormone therapy from the Million Women Study (325/100 000) and our control group (390/100 000). Unlike adherence to estrogen therapy, adherence to T therapy further decreased the incidence of breast cancer (73/100 000).ConclusionT and/or T + A, delivered subcutaneously as a pellet implant, reduced the incidence of breast cancer in pre and postmenopausal women. Evidence supports that breast cancer is preventable by maintaining a T to estrogen ratio in favor of T and, in particular, by the use of continuous T or, when indicated, T + A. This hormone therapy should be further investigated for the prevention and treatment of breast cancer.     

Results of treatment of breast cancer with tamoxifen]

There were 62 cases of mammary carcinoma treated with the antioestrogen tamoxifen. The age of the patients ranged from 35 to 75 years. Tamoxifen was administered in a daily dosage of 30 mg (3 x 1 tablet). Treatment was carried out as monotherapy or adjuvant therapy. Treatment was carried out for 6 months with a follow-up period of further 6 months. In the group of patients with mammary carcinoma, 23 were premenopausal without metastases after radical mastectomy and sterilisation. The remaining 39 in this group were in the menopause with metastases which were in some cases untreated and in some cases treated by mastectomy, radiation and chemotherapy (CMF-scheme). All Patients were PD in relation to further radiation and/or chemotherapy. Karnofsky-index was 60 minimum. After 4 weeks' treatment with tamoxifen both an improvement in general wellbeing and a regression of the focus of the tumour was achieved. A significant improvement in wellbeing and tumour status could be established for a total of 48 cases of mammary carcinoma. Treatment was well tolerated. Only 1 case of side effects in the form of vomiting occurred.     

血清外泌体miR-575与ER阳性乳腺癌患者他莫昔芬辅助治疗预后的相关性研究

目的研究血清外泌体miR-575水平与雌激素受体(ER)阳性乳腺癌患者他莫昔芬辅助内分泌治疗预后的相关性。方法通过生物信息学分析miR-575表达水平与乳腺癌患者总体生存率的关系。采集接受他莫昔芬辅助内分泌治疗的162例ER阳性乳腺癌患者的血液样本作为观察组,另外收集165例非癌志愿者的血液样本作为对照组,以实时荧光定量PCR法检测血清外泌体miR-575表达水平。观察组患者至少随访5年,根据患者对他莫昔芬的耐药情况将其分为抵抗组和敏感组,分析血清外泌体miR-575表达水平与术后疾病进展的关系。采用单因素和多因素Cox回归分析影响ER阳性乳腺癌患者他莫昔芬治疗预后的临床因素,并绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC)。结果生物信息学结果显示,miR-575在乳腺癌组织中的表达水平明显高于正常乳腺组织(P<0.001);且在ER阳性患者中,miR-575表达水平升高与Nottingham病理学分级较高以及预后不良有关(P<0.05)。观察组患者血清外泌体miR-575相对表达水平高于对照组1.834(1.168,2.519)vs.1.003(0.901,1.217),Z=-8.871,P<0.001;观察组患者血清外泌体与乳腺癌组织miR-575相对表达水平呈正相关(rs=0.726,P<0.001)。随访5年,110例患者对他莫昔芬耐药(抵抗组),52例对他莫昔芬敏感(敏感组)。抵抗组血清外泌体miR-575相对表达水平明显高于敏感组2.097(1.700,3.163)vs.1.168(0.947,1.524),Z=-7.164,P<0.001。Kaplan-Meier曲线显示,血清外泌体miR-575高表达组患者中位疾病进展时间短于低表达组(P<0.001)。Cox回归分析和ROC曲线结果显示,血清外泌体miR-575高表达是ER阳性乳腺癌患者接受他莫昔芬辅助内分泌治疗预后不良的独立危险因素(P<0.05),预测5年疾病进展的AUC为0.850(95%CI0.789~0.910)。结论血清外泌体miR-575表达水平较高预示着ER阳性乳腺癌患者接受他莫昔芬辅助内分泌治疗预后不良,有望成为预测他莫昔芬敏感性的一个重要参考指标。