Menopausal Breast Cancer Patients Research Articles

Long Noncoding RNAs-LET Behave as a Noncoding Signature for Early-Onset Menarche and Late-Onset Menopause in Breast Cancer Patients

Background: Breast cancer (BC) as a major cause of cancer-related death in women shows a very complex molecular and clinical phenotype, which has reduced the effectiveness of medical interventions. Evidence suggests that long noncoding RNAs (lncRNAs) are responsible for an important part of this complexity. This study aims to assess the expression and clinical implication of lncRNA LET in the pathobiology of BC. Materials and Methods: Quantitative real-time polymerase chain reaction was used to measure the expression of lncRNA-LET in breast tumors and adjacent normal-appearing tissues from 4 BC patients, as well as normal mammary tissues. Moreover, a bioinformatics approach was applied to uncover the potential lncRNA-LET-mediated sponge regulatory network as LET/miRNA/mRNA crosstalk. Results: Our study revealed that lncRNA-LET was significantly down-expressed not only in breast tumors but also in normal appearing breast tissues samples from BC subjects compared with true normal breast tissues obtained from healthy women. The low level of lncRNA-LET was meaningfully associated with early-onset menarche (≤13 years) and late-onset menopause (≥50) in patients. Moreover, the bioinformatics analyses support that lncRNA-LET could function as a tumor suppressor miRNA sponge. Conclusion: The results indicate that normal appearing breast tissues can undergo tumor-related molecular changes. Furthermore, they reveal the potential role of the dysregulation in LET-mediated ceRNA network in the pathophysiology of BC.

Phytoestrogen Treatment for Menopausal Vasomotor Symptoms after Breast Cancer

Introduction: In breast cancer patients, menopausal symptoms are often reached earlier and in a more severe manner than in healthy women. They can dramatically reduce a patient’s quality of life. Treatment for breast cancer patients remains difficult due to hormone replacement therapy being contraindicated. Therefore, treatment alternatives like herbal phytoestrogen preparations are considered to be a treatment option. Methods: All randomized controlled trials (RCTs) that investigated comparisons of food products, extracts, or dietary supplements containing phytoestrogens in women with a diagnosis of breast cancer were included in the analysis. Results: There was no evidence that phytoestrogen preparations had a benefit over placebo in the treatment of breast cancer patients with menopausal symptoms. Neither the frequency nor severity of menopausal symptoms and the quality of life or occurrence of adverse events were reduced in comparison to a placebo. Conclusion: As we cannot prove a benefit of plant extracts in the treatment of menopausal symptoms in breast cancer patients, different herbal preparations should be analyzed in RCTs in order to find sufficient and safe new treatment options for symptomatic menopausal breast cancer patients. A focus should also be laid on developing a core outcome set to simplify pooling of different studies.

Расширение возможностей лекарственной терапии климактерического синдрома у больных раком молочной железы

Objective. To study the effect of allogeneic placental therapy with Melsmon® on the quality of life of breast cancer (BC) patients with assessing possible risks of disease recurrence. Patients and methods. This study included 71 patients of reproductive age (38.3 ± 5.5 years) with invasive BC without signs of cancer grade 2–3 after complex treatment. All patients had a moderate-to-severe form of menopausal syndrome (MS). All women were divided into two groups: group I (study group, n = 33), in which human placenta hydrolysate (Melsmon®/Melsmon) was used to relieve menopausal symptoms; in group II (comparison group, n = 38), therapy with sedatives, vitamins, and phytotherapy were used. Allogeneic placental therapy with Melsmon® was used for 4 weeks (2 mL subcutaneously every other day (3 times a week)), then all patients received maintenance dosage: 2 mL subcutaneously twice a week for 8 weeks (total course of treatment was 12 weeks). Results. The study group (Melsmon®-therapy) showed a 3-fold decrease in vegetative disorders after 12 weeks, while this change was not observed in group II. There was a marked improvement in sleep quality in women in group I. The analysis of the stressors included in the approval list of the used psychodiagnostic method showed that stress reactions of respondents in group I in the form of anxiety, irritability, worries about uncontrollable life events, loss of confidence in the ability and possibility to solve personal problems were significantly lower than those in the women included in group II. During Melsmon®-therapy, positive dynamics of lipid profile in patients in group I was observed. Overall, a 1.8-fold decrease in triglyceride levels and 1.8-fold decrease in low-density lipoprotein levels were found in group I, with a 1.3-fold increase in high-density lipoproteins secretion. Conclusion. The results demonstrated the efficacy of MS treatment with human placenta hydrolysate, which contributed to a pronounced reduction in vegetative, metabolic, and psychological manifestations of MS. No recurrence of breast cancer was detected during the therapy period to date. The use of Melsmon®-therapy can expand the possibilities of drug therapy to improve the quality of life in menopausal breast cancer patients. Key words: breast cancer, menopausal syndrome, lipid profile, human placenta hydrolysate

Long Noncoding RNAs-LET Behave as a Noncoding Signature for Early-Onset Menarche and Late-Onset Menopause in Breast Cancer Patients

Background: Breast cancer (BC) as a major cause of cancer-related death in women shows a very complex molecular and clinical phenotype, which has reduced the effectiveness of medical interventions. Evidence suggests that long noncoding RNAs (lncRNAs) are responsible for an important part of this complexity. This study aims to assess the expression and clinical implication of lncRNA LET in the pathobiology of BC. Materials and Methods: Quantitative real-time polymerase chain reaction was used to measure the expression of lncRNA-LET in breast tumors and adjacent normal-appearing tissues from 4 BC patients, as well as normal mammary tissues. Moreover, a bioinformatics approach was applied to uncover the potential lncRNA-LET-mediated sponge regulatory network as LET/miRNA/mRNA crosstalk. Results: Our study revealed that lncRNA-LET was significantly down-expressed not only in breast tumors but also in normal appearing breast tissues samples from BC subjects compared with true normal breast tissues obtained from healthy women. The low level of lncRNA-LET was meaningfully associated with early-onset menarche (≤13 years) and late-onset menopause (≥50) in patients. Moreover, the bioinformatics analyses support that lncRNA-LET could function as a tumor suppressor miRNA sponge. Conclusion: The results indicate that normal appearing breast tissues can undergo tumor-related molecular changes. Furthermore, they reveal the potential role of the dysregulation in LET-mediated ceRNA network in the pathophysiology of BC.

A Clinicopathological Study of Pre and Post Menopausal Breast Cancer Patients in North Bengal Population & Their Correlation with Estrogen and Progesterone Receptor Status

A Clinicopathological Study of Pre and Post Menopausal Breast Cancer Patients in North Bengal Population & Their Correlation with Estrogen and Progesterone Receptor Status

Medical ovariectomy in menopausal breast cancer patients with high testosterone levels: a further step toward tailored therapy.

Five years of adjuvant therapy with anti-estrogens reduce the incidence of disease progression by about 50% in estrogen receptor-positive breast cancer patients, but late relapse can still occur after anti-estrogens have been discontinued. In these patients, excessive androgen production may account for renewed excessive estrogen formation and increased risks of late relapse. In the 50% of patients who do not benefit with anti-estrogens, the effect of therapy is limited by de novo or acquired resistance to treatment. Androgen receptor and epidermal growth factor receptor overexpression are recognized mechanisms of endocrine resistance suggesting the involvement of androgens as activators of the androgen receptor pathway and as stimulators of epidermal growth factor synthesis and function. Data from a series of prospective studies on operable breast cancer patients, showing high serum testosterone levels are associated to increased risk of recurrence, provide further support to a role for androgens in breast cancer progression. According to the above reported evidence, we proposed to counteract excessive androgen production in the adjuvant setting of estrogen receptor-positive patients and suggested selecting postmenopausal patients with elevated levels of serum testosterone, marker of ovarian hyperandrogenemia, for adjuvant treatment with a gonadotropins-releasing hormone analogue (medical oophorectomy) in addition to standard therapy with anti-estrogens. The proposed approach provides an attempt of personalized medicine that needs to be further investigated in clinical trials.

Abstract B251: Androgen receptor expression can predict benefit of tamoxifen treatment in patients with ER negative breast cancer.

Abstract The androgen receptor (AR) is frequently expressed in normal breast epithelium and in a substantial fraction of malignant breast tumors, even though the importance of AR in breast cancer is not established. In estrogen receptor (ER) positive breast cancer, AR binds to estrogen responsive element and inhibits proliferation, on the contrary in ER negative and HER2 positive cells AR activates the Wnt and HER2 pathways and induces proliferation. There are several therapies against the ER pathway and resistance to treatment is a big problem, targeting AR may be one alternative for some of these patients. In this study, we investigate the role of AR protein expression with immunohistochemistry in a defined cohort of 912 lymph node negative post menopausal breast cancer patients with a long follow up period randomized to no endocrine treatment or tamoxifen independent of ER expression, to examine if AR is a prognostic factor and/or predictor of tamoxifen treatment. In our cohort 82.4% showed AR expression in the tumour cells. In the case of ER positive patients without tamoxifen treatment, no significant difference was found when grouped by AR status (p>0.05). Tamoxifen treated patients with ER positive tumours showed benefit from the treatment regardless of AR expression (negative cases (p=0.038); positive cases (p=0.00001)). Further, if ER negative tumours from patients treated with tamoxifen were investigated AR expression was a tamoxifen predictive factor (p=0.014) (HR = 0.40 95% C.I. 0.18-0.89; p=0.024) but among cases with ER negative and AR negative tumours treatment with tamoxifen tended to have a worse outcome (p=0.06) HR = 2.26 95% C.I. 0.99-5.15; p=0.053. The multivariate interaction tests was significant (HR = 0.18 95% C.I. 0.056-0.56 p=0.003). There was a significant correlation between expression of the androgen receptor and small tumour size (p=0.002), PgR expression (p<0.001) ER expression (p<0.001), Cyclin D1 (p<0.001) and HOXB13 (p<0.001). The expression of AR was inversely correlated to HER2 (p=0.002). Tamoxifen is known to bind strongly to ER, however there are studies showing that tamoxifen also binds to AR. In prostate cancer, cell growth and AR activity were inhibited by tamoxifen and the ER antagonist fulvastrant effectively down regulates AR in several human prostate cancer cells and induce growth inhibition. These results suggest an anti-androgenic aspect of anti-estrogen. Our results indicate that AR is a tamoxifen predictive factor in ER negative breast cancer and suggest that this group of patients could benefit from tamoxifen treatment. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B251. Citation Format: Erik Hilborn, Jelena Gacic, Tommy Fornander, Lambert Skog, Bo Nordenskjöld, Olle Stål, Agneta Jansson. Androgen receptor expression can predict benefit of tamoxifen treatment in patients with ER negative breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B251.

Breast Cancer, Hormone Exposure, and Cognitive Function

Although published findings conflict, estrogen seems to have a beneficial effect on cognitive function. In contrast, breast cancer diagnosis has been associated with diminished cognitive function that has been attributed to the effects of adjuvant therapy. Investigators at a single U.S. institution compared medical histories, verbal intelligence, depressive symptoms, and cognitive function in 264 menopausal breast cancer patients before receiving adjuvant therapy (mean age, 61) with 95 healthy age- and …

Abstract P2-13-10: Prospective randomized and multicentric evaluation of cognition in menopausal breast cancer patients receiving adjuvant hormonotherapy: a phase III study (Preliminary results)

Abstract Background: Cognitive impairment has been considered to be a possible adverse effect of aromatase inhibitors (AI). The aim of the study was to compare the impact of tamoxifen or AI on verbal memory (Rey auditory-verbal learning test) and other cognitive functions (memory, executive and attentional functions) after 6 months of treatment. Methods: In this randomized, open-label phase III study, menopausal patients treated with adjuvant hormonotherapy for early breast cancer were enrolled at the end of the radiotherapy. Patients over 70 years, with a history of cognitive disorder or with prior chemotherapy were excluded. Detailed neuropsychological assessments and quality of life evaluations were performed before the 1st administration of hormonotherapy and then 6 months later. Considering the usual norms of the auditivo-verbal Rey test, an alpha risk of 5% and a 95% power, 27 patients per arm had to be included. Statistical analyses included Chi2 test and Student tests when appropriate. Results: 62 consecutive evaluable patients were randomized in 2 arms between March 2009 and April 2011. Patients received tamoxifen in arm A (n = 31) and AI in arm B (letrozole n=17; anastrozole n=12; exemestane n= 2). Median age at inclusion was 61.4 years. The median time since menopause was 10 years. Characteristics of the breast tumor and initial neuropsychological evaluations did not differ significantly between the 2 arms. After 6 months, we observed a significant decline of the performance at the episodic memory test (immediate recall of the Rey auditory verbal learning test) (p = 0.0015) in arm A only and a significant improvement on executive measures (Trail Making Test and Stroop test) (respectively p = 0.03/p = 0.002) in arm B. Quality of life didn't differ after 6 months of treatment. Conclusions: These preliminary results do not support that AI have a worse adverse effect on cognitive functions than tamoxifen after 6 months of treatment. A confirmation is planned after one year of treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-10.

Dream content and sleep changes in women after mastectomy.

e11524 Background: The concerns people express in their dreams are the concerns they have in waking life (Domhoff – Dreaming 11: 13-33; 2001) . In this abstract we report in breast cancer patients (BCP) the dream content, sleep quality and quantity , and their mood both before and after mastectomy (M), to determine whether a loss of a body part could change body schema and actuate a sexual sphere restructuring. Methods: Consecutive menopausal BCP without impaired cognitive impairment (MMSE < 24), without psychiatric and/or sleep disorders, not assuming drug that could affect REM sleep and waiting for M were enrolled. Pts were evaluated at T0 (7-10 days before M) and at T1 (3 months after M) with: 1) Dream Report Form (DRF – Domhoff , 1996) in which pts describe 5 recent dreams; 2) Dream Remind Questionnaire (DRQ) to obtain explicit content of dreams; 3) Beck Depression Inventory (BDI); 4) State Trait Anxiety Inventory , Form Y(STAI-Y). Results: Thirty pts were eligible: 15 pts dropped out (withdrew consent between T0 and T1); 15 pts completed the study (mean age = 51 yrs , range 45-66 yrs; education = 10 +/- 4 yrs). After M the total sleep time was significantly increased ( p<.05) ; sleep quality was unchanged .STAI and BDI were not significantly different. . At T1 we found a statistically significant increase in stated presence of wise self, determined self, curiosity, anger and shame. Excitement was reduced in T1.At T1 there is a reduction of violent and erotic environments, frightened-self perceptions, and repulsions, along with a slight increase of loved and powerful self-perception. In T1 dreams we found an increased presence of males and family characters, the proportion of dead people, striving elements with failure, a decreased presence of friends and aggressiveness. Torso-anatomy was significantly different in T1. Conclusions: Our results confirm a continuity between dreams and waking life. Dream content modifications are specifically related to body image.

Polymorphisms in adiposity-related genes are associated with age at menarche and menopause in breast cancer patients and healthy women

Is there any effect of genetic polymorphisms in adiposity-related genes on the timing of menarche and menopause and the total duration of menstruation among Korean women? Our results suggest that the adiposity-related genes LEP, LEPR and PPARγ may play a role in the onset and cessation of menstruation, and the total duration of menstruation. Previous candidate-gene approaches have mainly presented the results for genes related to the estrogen metabolism pathway. Most genes of interest that participate in steroid-hormone metabolism, such as estrogen receptor α and estrogen receptor β, have been associated with age at menarche and menopause. This study shows the possibility that adiposity-related genes also influence the duration of menstruation. We recruited 400 breast cancer patients and 452 healthy participants from a case-control study at the Center for Breast Cancer, National Cancer Center in Korea. Ten single nucleotide polymorphisms (SNPs) in the leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma (PPARγ) genes were investigated to evaluate their possible effects on menstruation. Associations between SNPs and age at menarche, age at menopause and duration of menstruation were evaluated. Four SNPs (rs2167270 of LEP, rs7602 of LEPR and rs4684846 and rs3856806 of PPARγ) were associated with late menarche (≥ 17-year-old). Four SNPs (rs2167270 of LEP and rs1801282, rs2120825, and rs3856806 of PPARγ) were associated with early menopause (<40-year-old) among post-menopausal women. In logistic regression models with covariate adjustment, women with the GG genotype of rs7602 (LEPR) had a higher risk for late menarche [odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.01-3.31] compared with their counterparts carrying the GA or AA genotypes. In addition, the GG genotype of rs2167270 (LEP) was inversely associated with a duration of menstruation of <30 years (OR = 0.59, 95% CI = 0.31-1.00) compared with the GA or AA genotypes. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: We obtained information on the age at menarche and menopause from self-administered questionnaires, and some participants might have had difficulty in remembering their age at menarche and menopause. However, this is a non-differential misclassification and should not appreciably affect the interpretation of the results of this study.

Transforming Growth Factor β Signaling Pathway Associated Gene Polymorphisms May Explain Lower Breast Cancer Risk in Western Indian Women

Transforming growth factor β1 (TGFB1) T29C and TGF β receptor type 1 (TGFBR1) 6A/9A polymorphisms have been implicated in the modulation of risk for breast cancer in Caucasian women. We analyzed these polymorphisms and combinations of their genotypes, in pre menopausal breast cancer patients (N = 182) and healthy women (N = 236) from western India as well as in breast cancer patients and healthy women from the Parsi community (N = 48 & 171, respectively). Western Indian women were characterized by a higher frequency of TGFB1*C allele of the TGF β T29C polymorphism (0.48 vs 0.44) and a significantly lower frequency of TGFBR1*6A allele of the TGFBR1 6A/9A polymorphism (0.02 vs 0.068, p<0.01) as compared to healthy Parsi women. A strong protective effect of TGFB1*29C allele was seen in younger western Indian women (<40 yrs; OR = 0.45, 95% CI 0.25–0.81). Compared to healthy women, the strikingly higher frequencies of low or intermediate TGF β signalers in patients suggested a strong influence of the combination of these genotypes on the risk for breast cancer in Parsi women (for intermediate signalers, OR = 4.47 95%CI 1.01–19.69). The frequency of low signalers in Parsi healthy women, while comparable to that reported in Europeans and Americans, was three times higher than that in healthy women from western India (10.6% vs 3.3%, p<0.01). These observations, in conjunction with the low incidence rate of breast cancer in Indian women compared to White women, raise a possibility that the higher frequency of TGFB1*29C allele and lower frequency of TGFBR1*6A allele may represent important genetic determinants that together contribute to a lower risk of breast cancer in western Indian women.

No Evidence of Increased Skin Toxicity with Aromatase Inhibitors and Concurrent Hypofractionated Radiation Therapy in Menopausal Breast Cancer Patients

No Evidence of Increased Skin Toxicity with Aromatase Inhibitors and Concurrent Hypofractionated Radiation Therapy in Menopausal Breast Cancer Patients

Body image disturbance and surgical decision making in egyptian post menopausal breast cancer patients.

BackgroundIn most developing countries, as in Egypt; postmenopausal breast cancer cases are offered a radical form of surgery relying on their unawareness of the subsequent body image disturbance. This study aimed at evaluating the effect of breast cancer surgical choice; Breast Conservative Therapy (BCT) versus Modified Radical Mastectomy (MRM); on body image perception among Egyptian postmenopausal cases.MethodsOne hundred postmenopausal women with breast cancer were divided into 2 groups, one group underwent BCT and the other underwent MRM. Pre- and post-operative assessments of body image distress were done using four scales; Breast Impact of Treatment Scale (BITS), Impact of Event Scale (IES), Situational Discomfort Scale (SDS), and Body Satisfaction Scale (BSS).ResultsPreoperative assessment showed no statistical significant difference regarding cognitive, affective, behavioral and evaluative components of body image between both studied groups. While in postoperative assessment, women in MRM group showed higher levels of body image distress among cognitive, affective and behavioral aspects.ConclusionBody image is an important factor for postmenopausal women with breast cancer in developing countries where that concept is widely ignored. We should not deprive those cases from their right of less mutilating option of treatment as BCT.

Circulating estradiol defines the tumor phenotype in menopausal breast cancer patients

Objective To correlate circulating hormone levels with the clinical and biological features of the tumors in menopausal breast cancer patients. Design Circulating hormone levels were measured in 161 previously untreated menopausal breast cancer patients within 72 h of their planned surgery. The obtained hormone levels were correlated with tumor size, histological and nuclear grade, histological score, axillary nodal status, DNA-ploidy and Ki67-, c-erb-B2-, p53, Bax-, VEGF- and Nup88-expression. Results The only statistically significant correlations found between circulating hormone levels and all tested variables were an inverse one between estradiol and the expression of the apoptosis-associated Bax gene ( p = 0.009), and again an inverse correlation between estradiol and the expression of c-erb-B2 ( p = 0.04). When comparing hormone levels with each other, a significant correlation between estradiol and progesterone ( p < 0.0001), an inverse one between estradiol and FSH ( p = 0.04) and a direct one between LH and prolactin ( p = 0.001) were found. Conclusion Higher circulating estradiol levels in postmenopausal breast cancer patients are associated with molecular features usually defining a biologically less aggressive tumor phenotype.

Weight change among breast cancer patients receiving chemotherapy: A retrospective analysis

19535 Background: Weight gain occurs in patients with early stage breast cancer receiving chemotherapy. The etiology is unknown. Most pre-menopausal patients receiving chemotherapy enter menopause during the course of treatment. We explored the relation between weight gain and development of menopause in breast cancer patients. We hypothesized that, among breast cancer patients receiving chemotherapy, those in the pre/perimenopausal group will gain more weight compared to postmenopausal group in the first 2 years. Methods: The electronic database at University of Arkansas was queried for breast cancer patients treated with chemotherapy between May 1992 and Nov 2003. Age, chemotherapy and weight at multiple time points (diagnosis, 6, 12, 24 and 60 months) were obtained. The mean weight changes across these time points were then calculated for the entire population and also after categorizing by age. Age was used as a surrogate for menstrual status. Women aged &gt;=50 yrs were considered postmenopausal, those &lt;50 yrs were considered pre or perimenopausal. Results: 617 patients were included in the analysis. There were 371 patients in the &gt;=50 age group and 246 patients in the &lt;50 age group. The average baseline weight for the entire population was 75.21 kg: 74.44 for women &lt;50 yrs and 75.71 for women &gt;= 50 yrs. Patients &lt;50 yrs of age gained weight in the first 2 yrs: 1.11 kg weight in the 1st year and 0.65 kg in the second yr. This was followed by loss of 1.19 kg over next 3 yrs which paralleled the loss of weight in the &gt;=50 group. The mean weight of the &gt;=50 age decreased by 0.27 kg in the first 2 years and then by 1.16 kg over the next 3 yrs following chemotherapy. Conclusions: Pre/perimenopausal breast cancer patients in our study gained weight, while postmenopausal patients had slight weight loss during the first 2 years. These findings imply that onset of menopause itself may be playing a significant role in weight gain among pre/perimenopausal breast cancer patients receiving chemotherapy. [Table: see text] No significant financial relationships to disclose.

Identifying menopause in breast cancer patients: considerations and implications

The pivotal role for oestrogen in the aetiology and progression of the majority of breast cancers is well established; consequently, endocrine therapy is an important approach in the treatment of this disease for many women. While tamoxifen has been the mainstay of endocrine therapy for breast cancer for over 30 years, we now have a range of therapeutic manipulations, in particular utilising the aromatase inhibitors (AIs) in post-menopausal women. To date each strategy employing an AI, including primary adjuvant monotherapy, switching from tamoxifen after 2-3 years, and extending adjuvant therapy with an AI after 5 years of tamoxifen, has shown superiority compared with tamoxifen alone; however, AI monotherapy is not suitable for pre- or peri-menopausal women, and therefore, an accurate assessment of the menopausal status of each individual patient is essential. Unfortunately, defining post-menopausal status can be fraught with difficulty, especially when cancer therapy is either recently completed (e.g. chemotherapy), or ongoing (e.g. tamoxifen and/or luteinising hormone-releasing hormone analogues). This paper shall review the definition of menopause in breast cancer patients and explore the issues and implications surrounding such a definition with respect to therapy choice for patient and physician alike.

Fulvestrant (F) in metastatic breast cancer: Standard dose (Std) vs loading dose (Ld)—A retrospective study

10575 Background: Fulvestrant is shown to be an effective hormonal agent in menopausal hormone-receptor positive metastatic breast cancer (MBC) patients. This study aimed at showing if Ld of fulvestrant will improve its efficacy over the FDA approved Std schedule. Methods: We retrospectively reviewed our pharmacy electronic database over a period of two years to identify MBC patients who were treated with fulvestrant. Patients received either Std of 250 mg IM on day (d) 1 and repeated Q28d or Ld of 500 mg IM d1 and 15 and Std on d28 which was repeated every 28 days until evidence of progression. All medical records were reviewed and responses were recorded as improved disease (ID), stable disease (SD), or progressive (PD) as documented by the treating oncologist. Time to response (TTR) (the interval from first injection until response) as well the duration of response (DR), was determined. Results: Medical records of 157 consecutive, evaluable patients who received F for their MBC were identified and reviewed. Group 1 (Gp1) received std (N = 122) and Group 2 (Gp2) received loading dose (N = 35). There were no significant differences between the two groups in relation to age, pathology, grade, Her-2, ER and PR status or number of prior chemotherapy regimens (p &gt; 0.05). Gp2 had statistically significant more prior hormone therapies (p = 0.0159). Median number of doses for Gp2 was 5 (R: 1–18) compared to 3 (R: 1–25) for Gp1 (p = 0.0169). Responses (ID) 14% for Gp1 and 18% for Gp2; clinical benefits (ID + SD) were 37.7% and 38%, respectively, NSS (p = 0.9550). TTR was 10 (R: 6–32) wks for Gp1 and 8 (R: 4–20) wks for Gp2; the DR was 15.5 (R: 4- 84) weeks for Gp1, and 12 (R: 2- 96) for Gp2. No statistical significance was detected between the 2 groups. Conclusions: This study showed there is no significant difference between the 2 dose schedules, either in the response rate or its duration. Prospective studies are needed to prove the equivalence of the Std and Ld of F. No significant financial relationships to disclose.

Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer

Objectives To estimate the pretreatment incidence of endometrial pathology and to prospectively assess the endometrial morbidity emerging during tamoxifen intake for breast cancer. Study design One-hundred and forty-six menopausal breast cancer patients, candidate to receive tamoxifen underwent endometrial assessment by Transvaginal Ultrasonography (TU) before the start of therapy. A double-layered endometrial stripe measuring more than 4 mm indicated hysteroscopy and endometrial biopsy. Endometrial abnormalities detected before the start of tamoxifen were treated by operative hysteroscopy or by hysterectomy; no therapy and yearly hysteroscopic follow-up was scheduled for patients showing non-atypical hyperplasias. All women were asked to undergo TU on a yearly basis; during the follow-up period, indication for hysteroscopy and endometrial biopsy were the following: (i) an endometrial lining measured above 4 mm at the first time, (ii) atleast a 50% increase of endometrial thickness since the last finding in patients previously assessed by hysteroscopy, (iii) a recorded vaginal bleeding, and (iv) previous findings of endometrial hyperplasia. Histopathologic result from biopsy or hysterectomy was the reference test to establish the baseline prevalence of endometrial pathology and the emerging prevalences of morbidity after 12, 24, 36, 48 and 60 months of tamoxifen therapy. Results One-hundred and five patients were followed for 60 months, whereas 113, 126, 137 and 141 patients were evaluated up to 48, 36, 24 and 12 months, respectively. In 44 out of 146 patients, pretreatment TU showed an endometrium thicker than 4 mm and in 31 (21.2%) of these patients abnormalities consisting of 16 endometrial polyps, seven polyps harboring simple hyperplasia, four simple hyperplasias, three atypical hyperplasias and one adenocarcinoma were found. During tamoxifen intake benign endometrial abnormalities were detected in 36 out of 114 assessable patients showing normal endometrium before the start of tamoxifen therapy (31.5%) and in seven out of 27 patients with baseline endometrial abnormalities (25.9%). Overall, an endometrial pathology emerged in 30.4% of patients during tamoxifen administration and in no patients we found an atypical lesion. Conclusions In menopausal breast cancer patients the incidence of endometrial abnormalities before the start of tamoxifen therapy is high and includes 2.7% of atypical pathology. After the diagnosis and treatment of baseline atypical lesions were accomplished, no atypical endometrial lesion emerged after the start of tamoxifen administration. Based on these findings, we believe that pretreatment assessment of endometrium is recommended in all menopausal women candidate to receive tamoxifen therapy.

Baseline endometrial assessment before tamoxifen for breast cancer in asymptomatic menopausal women

Objective. The aim of this study is to estimate the prevalence of endometrial pathology before the start of tamoxifen therapy in menopausal breast cancer patients. Methods. Ninety-one gynecologically asymptomatic patients, suffering from estrogen receptor-positive breast cancer and scheduled for adjuvant tamoxifen, underwent pretreatment endometrial assessment. In all patients, a transvaginal ultrasonography was carried out; a double-layered endometrial stripe measuring above 4 mm was considered as abnormal. In these patients, outpatient hysteroscopy and endometrial biopsy were performed. Pathologic findings were considered the reference test in estimating the prevalence of endometrial morbidity. Results. In 34 patients (37.3%) a thickened endometrium was an indication for hysteroscopic and pathologic assessment. Endometrial polyps, simple hyperplasias, and complex atypical hyperplasias were found in 10 (10.9%), 4 (4.3%), and 3 (3.2%) patients, respectively, leading to an overall prevalence of baseline endometrial morbidity of 18.6%. Established individual risk factors for development of endometrial pathology, such as body mass index, age at menarche and menopause, and parity, did not significantly differ in patients with and without endometrial abnormalities. Only patients' age (63.8 ± 8.6 and 52.2 ± 11.8; P = 0.03) and endometrial thickness (10.5 ± 3.5 and 3.9 ± 3.0; P > 0.001) were significant predictive factors of endometrial pathology. Conclusions. Menopausal women with estrogen receptor-positive breast cancer appear to have high risk of baseline subclinical endometrial abnormalities; therefore, an endometrial assessment, before the start of tamoxifen therapy, is always recommended in such patients.