Bone modifying agents in postmenopausal breast cancer patients treated with aromatase inhibitors: beyond bone protection?

Estrogen-receptor positive tumours represent the majority of breast cancers in postmenopausal women. Adjuvant endocrine therapy with aromatase inhibitors (AIs), continued for up to 10 years in high-risk patients, reduces by 40% the risk of recurrence. However, this therapy, among other side effects, is burdened with a higher incidence of osteoporotic bone fractures. To date, both bisphosphonates and denosumab are recognized as first-line drugs in the primary prevention of osteoporotic fractures in patients treated with AIs. They have demonstrated their effectiveness in increasing bone mineral density and in reducing the incidence of fractures, but they have also been shown to improve disease free survival (DFS).

Purified and specific cytoplasmic pollen extract: a non-hormonal alternative for the treatment of menopausal symptoms.

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin®. This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin® in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin®, an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin® may also be a suitable option for the management of menopausal symptoms in women with breast cancer.

Transvaginal high uterosacral ligament suspension: An alternative to McCall culdoplasty in the treatment of pelvic organ prolapse.

OBJECTIVES: Defects in female pelvic organ support are highly prevalent. Uterosacral ligament suspension at the time of primary prolapse repair (McCall culdoplasty) is a well-established surgical option to prevent prolapse recurrences. Recently Shull's high uterosacral ligament suspension technique has gained increasing popularity among Uro-Gynaecologists. A study carried out in 2017 by Spelzini et al. compared these two techniques, showing proper safety and efficacy in the treatment of prolapse, with no statistically significant differences as to operative time, complication rate, anatomical, functional and subjective outcomes [1]. Our study aims at comparing the effectiveness, complication rate, recurrence rate, quality of life and functional result of the two techniques. STUDY DESIGN: This is a retrospective study carried out on 224 patients who underwent vaginal cuff suspension for pelvic organ prolapse. Cases were extracted from hospital medical records of all women managed with surgical prolapse repair at our Gynaecology and Obstetrics department between January 2013 and February 2017. Shull suspension (group A) or McCall culdoplasty (group B) were performed according to surgeon's familiarity with the two suspension techniques. RESULTS: A total of 224 patients (69 in group A and 155 in group B) underwent surgical cuff suspension. Median operating time was 88 min for both techniques and ureteral injuries were very rare in both group A and B (1 and 0 respectively). In the evaluation of postoperative questionnaires, no statistically significant differences were found, except for "Urinary Impact Questionnaire" (UIQ), which showed significantly less urinary subjective symptoms in group A. Median follow up was 13 months in group A and 15 months in group B. Post-operative Pop-Q items analysis revealed only a higher Aa point in group A at 12 months follow up visit. Objective vaginal cuff recurrence was observed in 1 patient (1,4%) in group A and 4 patients in group B (2,6%) with no statistically significant difference between the two groups. CONCLUSIONS: Both uterosacral ligament suspension procedures are safe and highly effective. There were no statistically significant differences concerning surgical data, complication rates, and the majority of anatomical, functional and subjective outcomes between Shull suspension and McCall culdoplasty.

Day Surgery Management of Early Breast Cancer: Feasibility and Psychological Outcomes.

BACKGROUND/AIM: Breast cancer treatment represents a substantial amount of health-care costs and has a negative impact on womens' psychological health. Day-Surgery managment (DS) is a favorable alternative to a classic inpatient setting. In our prospective study we evaluated DS-treatment feasibility in terms of patient satisfaction, same-day-discharge rate, surgical-reintervention rate, psychological impact and costs. PATIENTS AND METHODS: We operated on 131 early breast cancer patients in DS. Surgical outcomes were evaluated. In 64 DS-treated breast cancer patients, psychological outcomes were analyzed using validated psychometric questionnaires and comparison was made with a corresponding group of women treated as inpatients. RESULTS: The same-day-discharge rate was 95.4%. No patient required readmission. The surgical-reintervention rate was 6.2%. DS-treatment significantly reduced anxiety (p=0.05) and depression (p=0.01) and afforded cost savings of 49%. CONCLUSION: DS-treatment of early breast cancer was feasible, with low reintervention rate, reduced anxiety and depression, high patients' satisfaction and substantial financial savings.

Impact of body mass index (BMI) on the prognosis of high-risk early breast cancer (EBC) patients treated with adjuvant chemotherapy.

The association between obesity and prognosis in early breast cancer (EBC) is unclear, especially when aggressive phenotypes are considered. We evaluated the influence of BMI on the prognosis of women with high-risk EBC enrolled in a phase III trial of adjuvant chemotherapy (CT). The association was assessed in 1066 patients with rapidly proliferating tumors, randomized to receive adjuvant CT with or without anthracyclines. Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier; multivariate analysis was performed according to age, tumor size, nodal, estrogen receptor (ER), and HER2 status and type of CT. Information on BMI was available for 959 women. Of these, 529 (55.2 %) were overweight or obese. Median age was 52 years. A total of 457 (47.7 %) patients had nodal involvement. Centralized pathology was performed in 850 cases: 522 (61.4 %) were ER positive, and 194 (22.8 %) were HER-2 positive. At a median follow-up of 103 months (range 1-188), 5-year DFS was 81 % (95 % CI 77-85), 82 % (95 % CI 77-86), and 76 % (95 % CI 70-83), in normal, overweight, and obese women, respectively (p = 0.44). Five-year OS was 92 % (95 % CI 89-95), 94 % (95 % CI 91-96), and 89 % (95 % CI 84-93), respectively (p = 0.60). BMI was not associated by multivariate analysis with differences in DFS or OS. Higher BMI had no influence on prognosis in high-risk EBC patients treated with CT. These data are consistent with prior observations and suggest that in aggressive biological subtypes, the impact of host factors on patient prognosis is minor.

Treatment of climacteric symptoms in survivors of gynaecological cancer.

Different treatments (surgery, radiotherapy, chemotherapy) for gynaecological cancers may cause ovarian failure or increase menopausal symptoms. There is a widespread reluctance among physicians to prescribe hormone replacement therapy (HRT) to the survivors of gynaecological cancer. This review analyses the use of HRT and of alternative therapies in such women. Squamous cervical cancer is not estrogen dependent and thus HRT is not contraindicated. While a cautious approach to hormone-dependent cancer is warranted, for women treated for non-hormone-related tumours alternative treatments for menopausal symptoms should be given due consideration, as any reluctance to prescribe HRT for them has neither a biological nor a clinical basis. In studies of HRT for survivors of endometrial and ovarian cancer, for instance, no evidence of increased risk was found, although no definitive conclusions can yet be formulated. The positive effect of HRT on quality of life seems to outweigh the unfounded suspicion of an increased risk of recurrence of non-hormone-related tumours. Effective non-hormonal alternatives for vasomotor symptoms are selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitors.

Randomized phase III trial of adjuvant epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) versus CMF followed by epirubicin in patients with node-negative or 1-3 node-positive rapidly proliferating breast cancer.

Adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) have proven highly effective in rapidly proliferating breast cancer (RPBC). It has also been seen that sequential administration of doxorubicin and CMF is superior to their alternation, especially in indolent tumors. In a phase III study, we evaluated whether adjuvant epirubicin (E) followed by CMF is superior to the inverse sequence in RPBC. Patients with node-negative or 1-3 node-positive RPBC (Thymidine Labeling Index > 3% or histological grade 3 or S-phase > 10% or Ki67 > 20%) were randomized to receive E (100 mg/m(2) i.v. d1, q21 days for 4 cycles) followed by CMF (600, 40, 600 mg/m(2) i.v. d1 and 8, q28 days for 4 cycles) (E â†’ CMF) or CMF followed by E (CMF â†’ E) or CMF for 6 cycles. From November 1997 to December 2004, 1066 patients were enrolled: E â†’ CMF 440, CMF â†’ E 438, and CMF 188. At a median follow-up of 69 months, 5-year OS was 91% (95% CI 88-94) for E â†’ CMF and 93% (95% CI 90-95) for CMF â†’ E, with adjusted hazard ratio of 0.88 (95% CI 0.58-1.35), and DFS was 80% in both arms, with adjusted hazard ratio of 0.99 (95% CI 0.73-1.33, Cox model). Adverse events were similar, apart from a higher rate of neutropenia in the CMF â†’ E arm. No important differences in clinical outcome were observed between the two different sequences, making both a valid option in early breast cancer. Further molecular characterization of the tumors might help to identify subgroups achieving higher benefit from either sequence.