Giulia Moggio

Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study

The study aim is to evaluate the efficacy and safety of two low-dose vaginal estrogen treatments (ETs) and of a non-hormonal vaginal moisturizer in postmenopausal breast cancer survivors with urogenital atrophy. Eighteen patients receiving estriol cream 0.25 mg (n = 10) or estradiol tablets 12.5 μg (n = 8) twice/week for 12 weeks were evaluated and compared with eight patients treated with polycarbophil-based moisturizer 2.5 g twice/week. Severity of vaginal atrophy was assessed using subjective [Vaginal Symptoms Score (VSS), Profile of Female Sexual Function (PFSF)] and objective [Vaginal Health Index (VHI), Karyopycnotic Index (KI)] evaluations, while safety by measuring endometrial thickness and serum sex hormones levels. After 4 weeks, VSS and VHI were significantly improved by both vaginal ETs, with further improvement after 12 weeks. PFSF improved significantly only in estriol group (p = 0.02). Safety measurements did not significantly change. Vaginal moisturizer improved VSS at week 4 (p = 0.01), but score returned to pre-treatment values at week 12; no significant modification of VHI, KI, PFSF was recorded. Both low-dose vaginal ET are effective for relieving urogenital atrophy, while non-hormonal moisturizer only provides transient benefit. The increase of serum estrogens levels during treatment with vaginal estrogen at these dosages is minimal.

Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications for diagnosis, surgical and medical treatment

A growing body of evidence support the association between the use of hormone replacement therapy (HRT) and a higher risk of both invasive lobular carcinoma (ILC) and invasive ductal-lobular mixed carcinoma (IDLC). Overall biological and clinical features of ILC entail a more cautious diagnostic and therapeutic approach as compared with invasive ductal carcinoma (IDC). ILCs are more frequently multifocal, multicentric and/or bilateral. Mammography and ultrasound show, therefore, significant limitations, while the higher sensitivity of magnetic resonance imaging in the detection of multifocal and/or multicentric lesions seems to improve the accuracy of preoperative staging of ILCs. Early diagnosis is even more challenging because the difficult in the localization and the sparse cellularity of lobular tumours may determine a false negative core biopsy. ILC is characterized by low proliferative activity, C-ErbB-2 negativity, bcl-2 positivity, p53 and VEGF negativity, oestrogen and progesterone positive receptors, low grade and low likelihood of lymphatic-vascular invasion. However, this more favourable biological behaviour does not reflect into a better disease-free and overall survival as compared with IDC. Since lobular histology is associated with a higher risk of positive margins, mastectomy is often preferred to breast conservative surgery. Moreover, only few patients with ILC achieve a pathologic response to preoperative chemotherapy and, therefore, in most patients mastectomy can be regarded as the safer surgical treatment. The preoperative staging and the follow-up of patients with ILC are also complicated by the particular metastatic pattern of such histotype. In fact, metastases are more frequently distributed to the gastrointestinal tract, peritoneum/retroperitoneum and gynaecological organs than in IDC.

Body mass index (BMI) and breast cancer: impact on tumor histopathologic features, cancer subtypes and recurrence rate in pre and postmenopausal women.

The study aims to analyze the association between body mass index (BMI) at time of diagnosis, breast cancer histopathologic features (tumor size, nuclear grade, estrogen and progesterone receptor (ER and PgR) and HER-2/neu expression, histological subtypes, Ki-67 index, lymphatic/vascular invasion, axillary nodes involvement) and incidence of different subtypes defined using hormone receptors and HER2/neu expression, according to menopausal status; to evaluate the impact of BMI on disease free survival (DFS) at multivariate analysis. A total of 2148 patients (592 premenopausal, 1556 postmenopausal) were classified into subgroups according to BMI distribution. High BMI was significantly associated with larger size tumor both in pre (p = 0.01) and postmenopausal women (p = 0.00). Obese premenopausal women showed worse histopathologic features (more metastatic axillary lymphnodes, p = 0.017 and presence of vascular invasion, p = 0.006) compared to under/normal weight group. Postmenopausal patients with BMI > 25 developed more frequently ER/PgR positive cancers (87% versus 75%, p 0.017), while no association was found in premenopausal women. We could not found any statistically significant correlation between breast cancer subtypes (luminal A, B, HER-2 and basal-like) and BMI both in pre and postmenopause. Higher BMI was significantly associated with a shorter DR-FS in postmenopausal women but the independent prognostic role of obesity was not confirmed in our analysis.

Non-hormonal treatment of hot flushes in breast cancer survivors: gabapentin vs. vitamin E

Objectives To assess the efficacy and the tolerability of gabapentin 900 mg/day compared to vitamin E for the control of vasomotor symptoms in 115 women with breast cancer. The secondary objective was to evaluate the effect of the treatments on the quality of sleep and other aspects of the quality of life. Methods A hot flush diary was completed daily; sleep quality and other menopausal symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI), the Menopause Rating Scale (MRS) and the SF-36 Health Survey. Results The prescribed treatment with gabapentin was never started by 28.3% of the patients and was interrupted by 28% for side-effects (dizziness and somnolence). Among the women allocated to vitamin E, 16.36% never started therapy and 34.78% dropped out because of inefficacy. Hot flush frequency and score decreased by 57.05% and 66.87%, respectively (p < 0.05) in the gabapentin group. The effect of vitamin E was fairly small: hot flush frequency and score were reduced by 10.02% and 7.28%, respectively (p > 0.05). Gabapentin was also particularly effective in improving the quality of sleep (PSQI score reduction: 21.33%, p < 0.05). Conclusion Gabapentin appears to be effective for the treatment of hot flushes with a favorable effect on quality of sleep. Vitamin E has only marginal effect on vasomotor symptoms.

Effects of tibolone on climacteric symptoms and quality of life in breast cancer patients—Data from LIBERATE trial

BACKGROUND Climacteric symptoms such as hot flushes and vaginal dryness are very common in breast cancer patients, resulting either from age or adjuvant therapy. Tibolone, a synthetic steroid, is effective in reducing these symptoms in healthy post-menopausal women, but this has never been studied in a large breast cancer population. OBJECTIVES The primary objective of LIBERATE trial was to study safety of tibolone 2.5mg daily versus placebo as primary, in symptomatic breast cancer survivors. The aim of this present paper was to report effects of tibolone on climacteric symptoms, vaginal dryness and health-related quality of life in the study population. This trial is registered with ClinicalTrials.gov, n. NCT00408863. METHODS The trial was conducted between June 2002 and July 2007. Concerning quality of life variables, a daily Diary Cards during the first three months and the Climacteric Symptoms Form and at each visit were used to register frequency and intensity of hot flushes. Mean vaginal dryness scores were calculated on the basis of individual ratings at baseline and at week 104. A subset of patients assessed their quality of life filling in the Womens Health Questionnaire (WHQ). RESULTS Of the 3148 women recruited, 3133 received trial medication (1575 in the tibolone group and 1558 in the placebo group). The median duration of treatment was 2.75 years. In total 3098 women (1556 on tibolone, 1542 on placebo) were included in the intention-to-treat (ITT) population for efficacy analysis. Data on vaginal dryness are available for 2144 patients and 883 women (438 on tibolone, 445 on placebo) answered to WHQ. The mean change in number of hot flushes per day was 2.74 (43.1%) in the tibolone group and -1.77 (-27.5%) in the placebo group (p<0.0001) at week 12 and -4.62 (-65.6%) on tibolone as compared to -3.73 (-52.5%) on placebo (p<0.0001) at week 104. For the composite score the mean changes at week 12 were -0.19 (-10.6%) and -0.14 (-7.7%), respectively (p=0.0006). Vaginal dryness score improved at week 104 in the tibolone group as compared to placebo (-0.46 versus -0.29, respectively; p<0.0001). Across the assessments up to two years with WHQ, tibolone was more effective than placebo in improving sexual health, sleep quality and mood domains. Women using tamoxifen showed less improvement in climacteric symptoms with tibolone, than women only receiving tibolone without any adjuvant therapy. CONCLUSION The results of the LIBERATE trial show that tibolone is effective in symptomatic breast cancer patients and improves their quality of life. However, this finding should be judged within the context of the main outcome of the trial, showing that tibolone increases the risk of recurrence. The use of tibolone in women with breast cancer will remain contraindicated and any off-label use incurs a now proven risk.

Transient ventricular hypocinesia after in utero anthracyclines exposure: a case-report and review of the literature.

Due to the low occurrence of cancer during pregnancy, limited data are available about outcome of infants exposed to chemotherapy in utero. We report the case of a newborn who developed transient ventricular hypocinesia and late-onset infection after in utero exposure to four epirubicin cycles for pregnancy-associated breast cancer. Moreover, we provide an overview of literature on neonatal outcome after anthracyclines-based chemotherapy regimen during pregnancy. Existing data support use of anthracyclines, as few cases of fetal cardiac toxicity were reported and most of short-term complications were transient. Need for prospective collection of data and longer follow-up is highly recognized.

Hormone-replacement therapy and lobular cancers: new deals and old myths

Luca Mariani, Claudio Robba, Giulia Moggio and Piero Sismondi Academic Department of Gynaecological Oncology, University of Turin Mauriziano Umberto I° Hospital of Turin & Institute for Cancer Research and Treatment of Candiolo, Turin, Italy “Several studies have reported that past and current users of combined hormone-replacement therapy are at a higher risk of developing invasive lobular carcinoma than invasive ductal–lobular mixed carcinoma.”

Retroperitoneal and Retrograde Total Laparoscopic Hysterectomy – Technique with Three- and Five-millimeter Trocars

In this chapter, we describe total laparoscopic hysterectomy (TLH) using retroperi‐ toneal and retrograde technique: it combines the retroperitoneal coagulation of the uterine artery and the retrograde approach to the pelvic organs, as in oncological surgeries. We report our experience in applying this modified TLH with 3-mm instruments and without uterine manipulator, in order to demonstrate its safety and feasibility.