Group Of Premenopausal Patients Research Articles

The long-term outcomes in perimenopausal patients treated for cervical cancer

Introduction. In the coming decades, the population of adults 65 years of age and older will increase significantly. Younger patients between 30 and 40 years of age, who are diagnosed with cervical cancer, have a better prognosis than the older group. The second peak of incidence, involving patients between 60 and 70 years of age, correlates with a poorer prognosis. Material and methods. In our study, we included 360 patients between 40 and 60 years old operated on due to cervical cancer followed by radiochemotherapy. We divided these patients into two groups according to age. The first group was composed of premenopausal patients (aged between 40 and 50 years) and the second of postmenopausal patients (aged between 50 and 60 years), and long-term outcomes (overall survival rates OS) were analysed in both groups of patients. Results. We observed statistically significant differences in the long-term outcomes between the subgroups of patients treated surgically for cervical cancer, and it was better in the premenopausal group of patients. No statistically significant relationship between these two groups of patients as far as clinical features was observed. Conclusion. We found that postmenopausal patients may actually benefit more from having radical surgery. Proving this supports the case for distinguishing geriatric oncology from gynaecological oncology.

Abstract 5644: The emergence of resistance to tamoxifen in relation to menopausal status, HER-2 status, status of steroid receptor and lymph nodes metastases status

Abstract Background: The study used data from medical and counselling of patients who were diagnosed with hormonedependent breast cancer. Aim: The objective of the paper is to identify within a group of patients diagnosed with hormone sensitive breast cancer and those who have received adjuvant tamoxifen, and then to isolate the patients with whom the therapeutic effect of tamoxifen stopped. Methods: The study analyzed 153 patients in the period from 2005 to 2011, at the Public Health Institution Hospital, Sveti Vračevi" in Bijeljina. Resistance to tamoxifen was developed by 60 patients (39.2%) and 93 patients (60.8%) did not develop resistance to it. Results: More common emergence of resistance is in the premenopausal group of patients (p<0.001). Statistically significant difference in frequency of resistance to tamoxifen was observed in the group of patients with ER-/PrR+ status of steroid receptors (p<0.001). In relation to HER-2 status of diagnosed cancer, a statistically significant difference in frequency of resistance emergence during tamoxifen therapy in patients with HER2-positive status (p<0.001) was observed. We found that there is a statistically significant difference between patients with metastatic in lymph nodes compared to patients who had no metastases in lymph nodes (X2=39.494; p<0.001). Conclusions: The analysis of menopausal status of patients, status of ER/PgR receptors status, HER-2 status of diagnosed cancer and status of lymph nodes trying to sort out the parameters on the basis of which a group of patients who can be expected to develop resistance to tamoxifen could be differentiated. Note: This abstract was not presented at the meeting. Citation Format: Sinisa Maksimovic. The emergence of resistance to tamoxifen in relation to menopausal status, HER-2 status, status of steroid receptor and lymph nodes metastases status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5644. doi:10.1158/1538-7445.AM2017-5644

Abstract OT3-2-06: TREND: A randomized phase II clinical trial evaluating the endocrine activity and efficacy of neoadjuvant degarelix versus triptorelin in premenopausal patients receiving letrozole for locally advanced endocrine responsive breast cancer (IBCSG 41-13)

Abstract Background The TREND trial compares endocrine activity of neoadjuvant triptorelin (Trip) and degarelix (Deg) in premenopausal patients receiving letrozole for primary endocrine responsive breast cancer. Recent studies suggest that combined neoadjuvant endocrine therapy with GnRH analogues and aromatase inhibitors (AIs) is effective for a selected group of premenopausal patients; degarelix, a GnRH antagonist, may induce faster ovarian suppression compared with other GnRH analogues. Trial Design This randomized phase II trial compares Trip and Deg in terms of time to optimal ovarian function suppression (OFS). The primary endpoint is defined as time from the first injection of Trip or Deg to the first assessment of centrally assessed 17-β-estradiol (E2) level in the range of optimal ovarian function suppression (≤2.72 pg/mL or ≤10 pmol/L) during the 6 cycles of neoadjuvant treatment. All patients receive 6 28-day cycles of neoadjuvant therapy: Trip: 3.75mg i.m. on day 1 of each cycle; Deg: 240mg s.c. cycle 1 day 1 and 80mg s.c. cycles 2-6 day 1. All patients receive 2.5mg/day continuous letrozole for all 6 cycles. Secondary endpoints include tolerability, Ki67 changes, preoperative endocrine prognostic index (PEPI) score, and best overall disease response. Major Eligibility Criteria • Premenopausal status confirmed (E2 > 54 pg/mL (or above 198 pmol/L) within 14 days of randomization • Histologically confirmed invasive breast cancer • ER and PgR > 50% of the cells and HER2-negative • No hormonal treatment in previous 2 months • No GnRH analogue, SERM or AI within 12 months prior to randomization • Normal hematologic, renal, liver and cardiac function Specific Aim To compare the endocrine activity of neoadjuvant Deg and Trip in premenopausal patients also receiving letrozole. Statistical Methods Randomized patients receiving at least one injection in both arms will be included in primary analysis. The primary endpoint will be evaluated in both treatment arms using stratified two-sample log-rank test (two-sided Type I error) with age as stratification factor. Assuming accrual of 25 patients per treatment arm (2 patients/month over approx. 24 months), the trial will have at least 90% power to detect a targeted or pre-specified difference in time to optimal OFS. Kaplan Meier method will be used to estimate distribution of the primary endpoint. Accrual: Target: 50 (Arm A: 25; Arm B: 25); Present: 0 Translational research A tumor block from the diagnostic core biopsy and one from final surgery will be collected and banked for central review and future translational research. Patient Reported Symptoms (PRS) PRS scores will be measured at baseline, day 1 of cycles 2 and 4 and prior to surgery. E2 will be correlated with the PRS scores. Individual endocrine symptoms (FACT-ES) will be summarized over time. Contact Information The TREND trial is conducted and sponsored by the International Breast Cancer Study Group (IBCSG). Contact Dr. Rudolf Maibach, IBCSG Coordinating Center, Bern, Switzerland, rudolf.maibach@ibcsg.org, or the Trial Coordinators at ibcsg41_TREND@fstrf.org. Pharmaceutical Support: Ferring. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-2-06.

Nuclear EGFR in ductal invasive breast cancer: correlation with cyclin-D1 and prognosis

The epidermal growth factor receptor (EGFR)-family and cyclin-D1 have been extensively studied in breast cancer; however systematic studies that examine protein expression and gene status in the same cohort of patients are lacking. Also emerging evidences suggest existence of a direct EGFR-signaling pathway, which involves cellular transport of EGFR from cell membrane to the nucleus, and transcriptional regulation of the target genes. Thus, we examined the protein expression of membrane EGFR, nuclear EGFR, cyclin-D1 and the corresponding gene status in 113 breast carcinomas by immunohistochemistry and fluorescence in situ hybridization using tissue microarrays. Membrane EGFR overexpression and EGFR gene amplification were detected in 2% cases, while nuclear EGFR was detected in 40% of cases, with 12% having high nuclear EGFR staining. Nuclear EGFR correlated with tumor size (P=0.0005), lymph node metastasis (P=0.0288), Nottingham prognostic index (P=0.0011) and estrogen receptor (ER) expression (P=0.0258) but the letter correlation was observed only in premenopausal group of patients. Strong cyclin-D1 expression and cyclin-D1 gene (CCND1) amplification were found in 64 and 13% of the cases, respectively. Cyclin-D1 expression showed positive correlation with ER (P=0.0113) and inverse correlation with Nottingham prognostic index (P=0.0309) and membrane EGFR (P=0.0201). CCND1 amplification also showed inverse correlation with membrane EGFR (P=0.0420). A strong correlation between membrane EGFR expression and gene amplification (P=0.0035), as well as cyclin-D1 overexpression and gene amplification (P=0.0362), was demonstrated. On univariate analysis cyclin-D1 expression showed a correlation with longer overall survival in the premenopausal group and nuclear EGFR correlated with shorter overall survival in whole cohort as well in the premenopausal group of patients. Multivariate analysis revealed nuclear EGFR to be an independent prognostic factor and showed 3.4 times greater mortality risk for nuclear EGFR+++ patients as compared with nuclear EGFR negative patients (hazard ratio =3.402; P=0.0026).

A randomised trial of goserelin versus control after adjuvant, risk-adapted chemotherapy in premenopausal patients with primary breast cancer – GABG-IV B-93

GABG-IV B-93 is a prospective, randomised study comparing goserelin ( n = 384) with no further treatment ( n = 392) in hormone receptor (HR)-negative breast cancer patients ( n = 465) after 3 cycles cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for patients with 0–3 positive lymph nodes (LN) or 4 cycles epirubicin, cyclophosphamide (EC) followed by 3 cycles CMF for patients with 4–9 positive LN. After completion of the ZEBRA trial the study was amended to enrol also HR-positive patients with 1–9 + LN ( n = 311). After a median follow-up of 4.7 years neither HR-negative nor HR-positive patients showed a benefit for goserelin. The adjusted estimated hazard ratio for event-free survival in HR-negative patients was 1.01 (goserelin versus control, 95% confidence interval [CI] 0.72–1.42, P = 0.97) and 0.77 in HR-positive patients (95% CI 0.47–1.24, P = 0.27). These results do not support the general use of goserelin after adjuvant chemotherapy in this group of premenopausal patients.

Breast F84The estrogen environment and Doppler parameters of breast lesions

BackgroundA high physiological variation of blood flow during menstrual cycle was found by examining breast vascularity with CW‐Doppler and is influenced by endocine therapy. In this study the correlation between the vascularity of breast lesions to menopausal status, phase of menstrual cycle and endocrine therapy is analysed.Method249 breast lesions in 91 premenopausal patients and 152 postmenopausal patients (142 malignant and 105 benign tumors) were demonstrated in B‐mode ultrasound and intratumoral vessels were visualized by color Doppler imaging. Bloodflow velocity waveforms were detected by pulsed Doppler. Correlations between the Doppler parameters Vmax, RI, PI, S/D and the number of intratumoral vessels (n) to the endocrine factors mentioned above were analysed.ResultsThe means of Doppler parameters in the group of premenopausal patients were: n = 1.38 (±1.53), RI = 0.69 (±0.09), PI = 1.25 (±0.36), S/D = 3.64 (±1.78), Vmax = 11.11 (±9.6) cm/s and in the postmenopausal group: n = 1.36 (±1.72), RI = 0.77 (±0.08), PI = 1.61 (±0.47), S/D = 5.08 (±3.21), Vmax = 11.04 (±6.4) cm/s. RI, PI and S/D‐values were significantly (P < 0.05) different between these two groups. The Doppler parameters of tumors examined in the follicular phase were similar to those in the luteal phase. During treatment with oral contraceptives the number of intratumoral vessels was higher n = 1.80 (±1.23) than during spontanous menstrual cycle n = 0.86 (±0.86).ConclusionMenopausal status and endocrine therapy have a robust influence on Doppler parameters of breast lesions.

Adjuvante Chemotherapie des Mammakarzinoms mit dem CMFV-Schema

Adjuvant CMFV therapy was administered from 1975 to 1984 at the Department of Gynaecology and Obstetrics of the University of Erlangen in 331 patients from a patient population, who underwent an operation with the intention of curing invasive breast cancer. Six cycles of this therapy were administered to 224 women. Only these patients were considered in the evaluation. 538 patients without axillary lymph node metastases and without adjuvant therapy served as reference population. The significance of adjuvant CMFV therapy in relation to the lymph node and menopausal status was investigated in a retrospective analysis. It was shown, that the five-year actual survivals in the group of premenopausal patients with one to three affected lymph nodes and CMFV therapy (n = 60), did not differ significantly from the group of women with premenopausally negative lymph nodes without adjuvant therapy (n = 198) (87.7% versus 88.2%). On the other hand, in the postmenopausal patients, the five-year actual survivals for the corresponding groups were 65.9% and 83.2%, respectively. The difference was significant. The results indicate, that adjuvant CMFV therapy improves the prognosis in premenopausal women, above all in cases with one to three affected lymph nodes. In the postmenopausal patients, a comparable effect could not be demonstrated in this group of patients.

EFFECT OF HYSTERECTOMY, OOPHORECTOMY AND ESTROGEN THERAPY ON LIBIDO

The effect of hysterectomy with and without bilateral oophorectomy and subsequent estrogen replacement on libido was investigated in 85 women. All were aged 45-55 years and had no general disease or other diagnosed disorder. Controls were a group of premenopausal patients with intact uterus and ovaries. Because the group was small a computer was used to help determine statistical significance of findings. All patients undergoing hysterectomy irrespective of whether the ovaries had been conserved or not had a high incidence of decreased or absent libido. Replacement estrogen therapy was not of any value in its treatment. This is even more surprising in view of the proven mental tonic effect of exogenous estrogen therapy as found by others. The cause of this decreased libido is beyond the scope of the present study but a psychological response to the operation of hysterectomy per se cannot be excluded.