Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

OBJECTIVES: Nodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition. Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. METHODS: Clinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. RESULTS: Fifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case. Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT. Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. CONCLUSIONS: In this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

Impact of Pregnancy on Breast Cancer Features and Prognosis.

BACKGROUND: pregnancy-associated breast cancer (PABC) affects one in 3000 pregnancies, often presenting with aggressive features. METHODS: We retrospectively evaluated a cohort of 282 young BC patients (≤45 years old) treated between 1995 and 2019, dividing them into three groups: nulliparous women, women with PABC (diagnosed within 2 years since last pregnancy) and women with BC diagnosed > 2 years since last pregnancy. This last group was further stratified according to the time between pregnancy and BC. The analysis encompassed histological factors (tumor size, histotype, grading, nodal involvement, multifocality, lympho-vascular invasion, hormone receptor expression, Ki-67 index, and HER2 expression), type of surgery and recurrence. RESULTS: Age at diagnosis was younger in nulliparous than in parous women (p < 0.001). No significant differences were noticed regarding histological characteristics and recurrences. At univariate analysis, nodal involvement (OR = 2.4; p < 0.0001), high tumor grade (OR = 2.6; p = 0.01), and lympho-vascular invasion (OR = 2.3; p < 0.05), but not pregnancy (OR = 0.8; p = 0.30), influenced DFS negatively. Multivariate analysis confirmed nodal involvement as the only negative independent prognostic factor for a worse DFS (OR = 2.4; p = 0.0001). CONCLUSIONS: in our experience, pregnancy is not an independent adverse prognostic factor for BC DFS.

Factors associated with adherence to BRCA1/2 mutation testing after oncogenetic counseling in long-surviving patients with a previous diagnosis of breast or ovarian cancer.

BRCA1/2 mutations account for 5 to 10% of breast and 15% of ovarian cancers. Various guidelines on BRCA1/2 genetic counseling and testing have been issued, and the criteria have evolved over the years. Oncogenetic counseling aims to inform patients about the possibility and implications of undergoing predictive testing and risk management programs. We analyzed a cohort of 50 subjects with a previous personal history of breast or ovarian cancer who had not been tested for BRCA1/2 mutations at the time of diagnosis but were found eligible according to the most recent guidelines. All patients were offered pre-test oncogenetic counseling and BRCA1/2 genetic testing. The mean time from cancer diagnosis to genetic counseling was over 10 years. We analyzed socio-demographic and psychological parameters associated with the decision to undergo BRCA1/2 genetic testing or the reasons behind the withdrawal. Thirty-nine patients underwent BRCA1/2 genetic testing. Patients who accept the genetic test communicate more easily with family members than those who refuse. Factors associated with test refusal are having a long-term partner and having a negative perception of life. There is a trend, although not statistically significant, toward younger age at cancer diagnosis, more likely to participate in cancer screening programs (71.8% vs. 45.5%), and more likely to have daughters (63.3% vs. 37.5%) in the group that accepted the test. The offer of BRCA testing was well accepted by our study population, despite the many years since the cancer diagnosis. With the perspective of further broadening the access criteria to genetic testing, it is important to understand how to best approach pre-test counseling in long-surviving patients with a previous diagnosis of cancer.

Straining to void at preoperative urodynamic study as a risk factor for prolapse recurrence after surgery.

OBJECTIVES: Straining to void is the need to make a muscular effort in order to initiate, maintain or improve the urinary stream, through an increase in abdominal pressure. This pattern of bladder emptying is frequently observed in women with pelvic organ prolapse causing urinary obstruction, to overcome the increased resistance to urine flow. However, frequent increases in abdominal pressure are a risk factor for developing pelvic organ prolapse, and might play a role in its recurrence after surgery. The aim of this study was to investigate the role of straining identified at urodynamic study in prolapse recurrence after surgical repair. STUDY DESIGN: This was a retrospective study on women submitted to prolapse repair by vaginal hysterectomy with modified McCall culdoplasty and anterior colporraphy. All patients underwent a preoperative urodynamic evaluation including a pressure-flow study performed after prolapse reduction by means of a vaginal pessary; straining was defined by a simultaneous and similar increase in intravesical and abdominal pressures of at least 10 cmH2O over the baseline during bladder emptying, corresponding to intermittent peaks of urine flow. Patients were divided into two groups according to the presence or absence of straining, and they were compared for surgical results at 12 months and for the rate of anterior or central recurrence over time. RESULTS: Women with straining (n = 16), compared to women with normal voiding (n = 43), showed a higher risk of anterior recurrence over time at Kaplan-Meier curves, for both stage II (p = 0.02) and stage III prolapse (p = 0.02). No difference was seen for central recurrence during the follow up period. POP-Q staging at 12 months was similar for the two groups, except for the location of the Aa point which was significantly better for women without straining (-1.6 ± 0.1 cm vs -0.8 ± 0.3 cm, p = 0.03). CONCLUSIONS: Straining to void identified in preoperative urodynamic study seems to increase the risk of anterior recurrence after surgical repair of pelvic organ prolapse.

Retrospective study of histopathological and prognostic characteristics of primary fallopian tube carcinomas: twenty-year experience (SOCRATE).

OBJECTIVE: Primary fallopian tube carcinoma represents a rare entity, accounting for about 0.75%-1.2% of all gynecological malignancies. The rationale of our study is to describe the prognosis of primary fallopian tube carcinoma. METHODS: We retrospectively identified patients with FIGO stage I-IV, all histology types and grading primary fallopian tube carcinoma treated in three major oncological centers between January 2000 and March 2020. Exclusion criteria were bulky tubo-ovarian carcinomas, isolated serous tubal intraepithelial carcinoma or neoadjuvant chemotherapy. RESULTS: A total of 61 patients were included. The vast majority of primary fallopian tube carcinomas were serous (96.7%) and poorly differentiated (96.7%) and arose from the fimbriated end of the tube (88.5%). Larger tumor size correlated with higher probability of correct preoperative differential diagnosis of primary fallopian tube carcinoma (p=0.003). Up to 82.4% of patients with small tumors (≤15 mm) presented with high FIGO stage (≥IIA). The most common site of metastasis was pelvic peritoneum (18.8%) and among 59% of patients who underwent lymphadenectomy smaller tumors had higher rate of nodal metastasis (42.9%≤10 mm vs 27.3%>50 mm). After 46.0 months of mean follow-up there were 27 recurrences (48.2%). The most common site of relapse was diffuse peritoneal spread (18.5%). The 5-year disease-free survival was 45.2% and 5-year overall survival was 75.5%. Of note, 42.9% of patients with stage IVB survived >36 months. CONCLUSION: Primary fallopian tube carcinoma is a biologically distinct tumor from primary epithelial ovarian carcinoma and it is mostly located in the fimbriated end of the tube. In addition, it is characterized by a high rate of retroperitoneal dissemination even at apparently an early stage and its size does not correlate with FIGO stage at presentation.

Fixation of uterosacral ligaments to anterior vaginal wall during modified McCall culdoplasty after vaginal hysterectomy.

OBJECTIVES: McCall culdoplasty is a commonly performed procedure for pelvic organ prolapse surgical repair; despite its good efficacy, however, anterior prolapse recurrence frequently occurs. The aim of our study was to verify whether fixation of utero-sacral ligaments (USLs) to anterior vaginal wall during a modified McCall culdoplasty (MMC) could reduce the rate of anterior recurrence of prolapse. STUDY DESIGN: This was a retrospective study on women submitted to MMC after vaginal hysterectomy and anterior colporraphy for prolapse repair. Patients undergoing concurrent anterior fixation of USLs (AF) were compared to cases treated with MMC alone, evaluating potential differences in anatomic result of prolapse repair at 12 months, rate of anterior recurrence over time, operative data and post-operative morbidity. RESULTS: Women undergoing MMC with AF (n = 45), compared with patients treated with MMC alone (n = 77), showed better results in terms of anatomic support in the anterior compartment at 12 months, assessed by means of POP-Q system parameters Aa (-1.8 cm vs -1.2 cm, p 0.0025) and Ba (-2.0 cm vs -1.3 cm, p 0.00015), and a lower rate of anterior recurrence (11.1% vs 29.9%, p 0.025); the other parameters of prolapse anatomic staging did not differ significantly, nor did operative data or post-operative morbidity. Follow up confirmed a longer disease-free survival over time for women treated with MMC with AF (p 0.028) CONCLUSIONS: Fixation of USLs to anterior vaginal wall at time of post-hysterectomy MMC appears to improve anatomic outcomes of the procedure reducing the risk of anterior prolapse, without implying a reduced safety, nor a greater surgical complexity.

Potential effectiveness of Ospemifene on Detrusor Overactivity in patients with vaginal atrophy.

OBJECTIVES: To report the effects on the urinary function of ospemifene prescribed for vulvovaginal atrophy (VVA) in patients with overactive bladder (OAB) symptoms refractory to the first line of pharmacologic treatment with antimuscarinic or ß3-agonists drugs. We also try to identify any predictors of response to the ospemifene treatment. STUDY DESIGN: Twenty-five patients with OAB confirmed by detrusor overactivity at urodynamics, refractory to first-line therapy for OAB, were enrolled for the study. All of them received ospemifene 60 mg for 12 weeks because of concomitant VVA. We performed a clinical examination, a 3-day voiding diary, ultrasound examination of bladder wall thickness (BWT), and evaluation by Visual Analogic Scale (VAS) of vaginal dryness at baseline and at 12 weeks. We evaluated urinary symptoms and their impact on the quality of life with UDI-6 SF and OAB-Q (Qol, sf) questionnaires. RESULTS: After 12 weeks of treatment, we observed a significant reduction in the daily (24 h) numbers of episodes of micturition, of nocturia, of urgency and of incontinence. We also found a significant reduction in BWT and vaginal dryness, together with an improvement of OAB-Q and UDI6 SF scores. Among patients who subjectively benefited from the treatment, we found a baseline lower prevalence of constipation and a higher degree of vaginal dryness. CONCLUSIONS: Ospemifene might be a useful option for postmenopausal women with VVA and OAB symptoms, refractory to the first line of treatment with ß3-agonists or antimuscarinic drugs, before considering invasive options.

Concomitant stress urinary incontinence and pelvic organ prolapse surgery: Opportunity or overtreatment?

OBJECTIVES: The association between pelvic organ prolapse (POP) and stress urinary incontinence (SUI) is very common. When POP surgery is indicated and the patient has concomitant SUI, there are two treatment strategies: the one-step strategy (concomitant correction of POP and SUI) and the two-step strategy (correction of POP with subsequent evaluation of SUI). Guidelines from the International Continence Society and International Consultation on Incontinence recommend that a urodynamic assessment (UA) should be performed before surgery as this can reveal the presence of urodynamic SUI, but the role of UA is the subject of debate as it does not seem to improve treatment decisions. The aim of this study was to identify the presence of pre-operative urodynamic parameters that were predictive of POSUI, and to identify patients who could benefit from concomitant correction of SUI during POP surgery STUDY DESIGN: A retrospective evaluation was undertaken of 155 patients with at least second-degree POP who underwent POP surgery after UA between 2009 and 2016 in an Italian gynaecology and obstetrics department. Of these, 61 patients were clinically incontinent before surgery and 94 patients were clinically continent. After UA, patients were stratified using a maximum urethral closure pressure (MUCP) cut-off of 50 cmH2O; the risk of POSUI was calculated using this value. RESULTS: POP surgery alone resolved SUI in 60 % of the 61 clinically incontinent patients; only 30 % of these patients had urodynamic SUI and >50 % did not have POSUI. Thirty-six percent of the 94 continent patients had occult SUI on UA and 16 % developed de-novo POSUI. Seventy-five percent of all patients with occult SUI did not develop de-novo SUI. MUCP was lower in patients with POSUI than in patients without POSUI (p=0.013). The probability of POSUI was higher in patients with MUCP ≤50 cmH2O. The number needed to treat (NNT) to prevent one case of POSUI in these patients was 2, compared with an NNT of 4 in the continent group. Eight percent of patients underwent further surgery for SUI. CONCLUSIONS: Clinically incontinent patients with MUCP ≤50 cmH2O will gain the greatest benefit from concomitant POP and SUI surgery. However, concomitant surgery has more severe adverse events. Given that 62.3 % of patients resolved SUI after POP surgery alone, it is important not to overtreat these women. Clinical pre-operative SUI is the best indicator of POSUI and was found to increase the risk of POSUI (odds ratio 3.2, 95 % confidence interval 1.5-6.8; p=0.003). Despite the small sample size, the two-step strategy appears to result in lower use of mid-urethral slings and a clear reduction in complications. It is important not to focus on the diagnosis of urodynamic SUI in continent patients but to evaluate MUCP carefully.

Metastatic Bilateral Strumal Carcinoid: A Case Report and Review of the Literature.

Primary ovarian carcinoids are very rare tumors that belong to the germ cell family of ovarian malignancies. They account for less than 1% of all carcinoid tumors and for less than 0.1% of all ovarian neoplasms. Recurrences are even rarer, with only few cases reported in the literature. Strumal carcinoid has recently been recognized as an extremely rare distinct entity. We report on a patient with bilateral mature cystic teratoma with millimetric foci of ovarian strumal carcinoid who developed lymph node para aortic metastasis after 30 years from primary diagnosis. Our case is thus far the second report of a metastatic strumal carcinoid and the first one in which strumal carcinoid occurred bilaterally and was also metastatic.

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.

Breast cancer treatment in mutation carriers: surgical treatment.

The surgical option which should be reserved for patients with BRCA1/2 mutation and breast cancer diagnosis is still debated. Several aspects should be considered before the surgical decision-making: the risk of ipsilateral breast recurrence (IBR), the risk of contralateral breast cancer (CBC), the potential survival benefit of prophylactic mastectomy, and the possible risk factors that could either increase or decrease the risk for IBR or CBC. Breast conservative treatment (BCT) does not increase the risk for IBR in BRCA mutation carriers compared to non-carriers in short term follow-up; however, an increased risk for IBR in carriers was observed in studies with long follow-up. In spite of the increased risk for IBR in patients who underwent BCT than patients with mastectomy, no significant difference in breast-cancer specific or overall survival was observed by local treatment type at 15 years. Patients with BRCA mutation had a higher risk for CBC compared with non-carriers and BRCA1-mutation carriers had an increased risk for CBC compared to BRCA2-mutation carriers. Bilateral mastectomy is intended to prevent CBC in BRCA mutation carriers, however, no difference in survival was found if a contralateral prophylactic mastectomy was performed or not. For higher-risk groups of BRCA mutated patients, a more-aggressive surgical approach may be preferable, but there are some aspects that should be considered in the surgical decision-making process. The use of adjuvant chemotherapy and performing oophorectomy are associated with a decreased risk for IBR. When considering the risk for CBC, three risk factors were associated with significantly decreased risk: the use of adjuvant tamoxifen, performing oophorectomy and older age at first breast cancer diagnosis. As a result, we could identify a group of patients that might benefit from a more aggressive surgical approach (unilateral mastectomy or unilateral therapeutic mastectomy with concomitant contralateral prophylactic mastectomy). For women with BRCA mutations candidate to mastectomy, preservation of the nipple-areola complex (NAC) may be highly important due to the generally younger age at time of surgery. Concerning the oncological safety, nipple sparing mastectomy (NSM) is an acceptable option, with no evidence of compromise to oncological safety at short-term follow-up. The evaluation of surgical treatment in breast cancer patients with BRCA 1/2 mutation, should include several issues, namely the current evidence of adequate oncological safety of BCT in BRCA mutated patients; the increased risk for CBC especially in BRCA1 carriers; the feasibility on NSM with a greater patient's satisfaction for cosmetic results with no evidence of compromised oncological safety and, finally, the awareness that breast radiotherapy might increase the risk of complications in a possible subsequent mastectomy with immediate breast reconstruction.

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.

Genitourinary Syndrome of Menopause in Breast Cancer Survivors: Are We Facing New and Safe Hopes?

Breast cancer survivors (BCSs) often suffer from menopausal symptoms induced by systemic treatments, with a consequent negative effect on quality of life. Since the introduction of aromatase inhibitors as the standard therapy for hormone-dependent tumors, genitourinary syndrome of menopause (GSM) has become a main problem for BCSs. This new terminology refers to the wide range of vaginal and urinary symptoms related to menopause, which can be relieved by estrogen therapy. Unfortunately, systemic hormone therapy is contraindicated for BCSs and also vaginal estrogens at standard dosage might influence the risk of recurrence because they cause a significant increase of circulating estrogens. Nonhormonal vaginal moisturizers or lubricants are the first choice for BCSs but only have limited and short-term efficacy. New strategies of management of GSM are now available, including: (1) low-dose or ultra low-dose vaginal estrogens; (2) oral selective estrogen receptor modulators (ospemifene); (3) androgen therapy; (4) physical treatment with vaginal laser; and (5) psychosocial interventions. In this review we discuss and analyze these different options.

Granulocyte-colony stimulating factor upregulates ErbB2 expression on breast cancer cell lines and converts primary resistance to trastuzumab.

The recombinant monoclonal antibody trastuzumab has antiproliferative effect on breast cancer (BC) cells with ErbB2 overexpression. We postulated that a mechanism able to modify ErbB2 expression enhances the antitumor effect of trastuzumab. We analyzed whether granulocyte-colony stimulating factor (G-CSF), widely used in adjuvant cancer therapy to alleviate chemotherapy-induced myelotoxicity, could influence ErbB2 expression in BC cells and patients. The expression of ErbB2 (Herceptest) was analyzed in four BC cell lines (BT474, SKBR3, ZR75.1, and T47D) treated with G-CSF and in five samples biopsies from BC patients subjected to G-CSF rescue after chemotherapy. The effects of G-CSF and trastuzumab alone or their combination on cell growth and apoptosis were investigated. G-CSF receptor was detected on all cell lines and BC patients. G-CSF induced upregulation of ErbB2 in SKBR3, ZR75, and T47D cells. This modulation was not associated with an increase in tumor cell growth in vitro. Trastuzumab alone inhibited colony formation in soft agar but did not induce apoptosis on BC cells with no or low ErbB2 genomic amplification. The combination of trastuzumab and G-CSF enhanced the inhibition of tumor colony formation and induced apoptosis on these cells. This effect was further increased by G-CSF pretreatment. Five of nine BC patients showed an increase of Herceptest score after G-CSF administration. G-CSF treatment increases ErbB2 expression in vitro and in vivo enhancing the activity of trastuzumab on BC cell lines inducing apoptosis of BC cells with low or no ErbB2 genomic amplification.

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.

Modification of serum IGF-I, IGFBPs and SHBG levels by different HRT regimens.

UNLABELLED: During the menopause, levels of SHBG, IGF-I and IGFBPs are significantly modified by the use of different HRT regimens. OBJECTIVE: The aim of this study is to evaluate the influence of three different HRT regimens on serum levels of SHBG, IGF-I, IGFBP-1 and IGFBP-3 in postmenopausal women. METHODS: 41 postmenopausal women requesting HRT were enrolled in the study. Subjects were divided in three groups according to the therapy assigned; Group A: estradiol 2 mg/day+cyproterone acetate 1 mg/day in a cyclic sequential regimen; Group B: estradiol hemihydrate 2 mg/day plus norethisterone acetate (NETA) 1 mg/day in a continuous combined regimen; Group C: estradiol hemihydrate 1 mg/day plus NETA 0.5 mg/day in a continuous combined regimen. Blood samples were drawn before the start of hormonal treatment and after 6 months of HRT. Levels of SHBG, IGF-I, IGFBP-1 and IGFBP-3 in the serum were measured by means of a specific immunoassay. RESULTS: In group A, a significant increase of SHBG, no change of IGFBPs and a significant decrease of IGF-I were observed; in group B and in group C, no significant variations for any of the parameters were recorded. CONCLUSIONS: The association of cyproterone acetate to oral estradiol determines a significant reduction of IGF-I levels and an increase of SHBG; nevertheless, it does not seem to influence the serum levels of the IGF-I binding proteins. The treatment with oral continuous combined estrogens plus androgenic progestins, at low doses, produces minor, not significant, changes in the circulating levels of IGF-I, SHBG and IGFBPs.