Time-varying effect and long-term survival analysis in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time. METHODS: Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length. RESULTS: The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The 'prognostic benefit' of low-grade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1-0.4) at 6 months to 2.2 (95% CI 1.3-3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1-2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4-1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group. CONCLUSION: From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.

Impact of Surgery on the Evolution of Uterine Sarcomas.

STUDY OBJECTIVE: To identify the characteristics of uterine sarcomas and assess the impact of morcellation on prognosis. DESIGN: Case-control study. (Canadian Task Force classification II-2). SETTING: Hospital Quiron-Dexeus, an academic hospital. PATIENTS: Patients with uterine sarcoma histologically diagnosed and treated in our center between 1987 and 2013. INTERVENTION: All descriptive data, including type of surgery and clinical and pathological data, were reviewed. Survival analysis was performed comparing patients with hysterectomy/myomectomy without any type of morcellation and patients with morcellation during surgery. MEASUREMENTS AND MAIN RESULTS: A total of 37 sarcomas were diagnosed during the study period. The most common symptom was metrorrhagia (50%). The indication for surgery was related to myoma growth in 40% of cases and to metrorrhagia in 37.1% of cases. Open surgery was performed in 23 patients (62.2%), and laparoscopy was performed in 9 (24.3%). Myomectomy was performed in 14 patients (37.8%), and 23 patients (62.1%) underwent hysterectomy as initial surgery. Morcellation for tumor extraction was done in 8 cases (21.6%). Survival analysis by surgical approach showed increased disease-free survival (DFS) in the laparotomy group compared with the laparoscopy group (median, 70.3 months vs 10.4 months; p = .018). Median DFS according to type of surgery was 6.3 months in morcellation cases, 11.9 months in vaginal fragmentation cases, and 149.9 months in nonmorcellated cases (p < .002). The median time to progression was shorter in morcellated cases (laparocopic and vaginal) compared with nonmorcellated cases (11.9 vs 14.9 months; p < .001). No statistically significant differences in prognosis were related to myomectomy versus hysterectomy; however, there were significants difference between morcellation and nonmorcellation cases. CONCLUSION: Taking into account the negative impact of morcellation in sarcomas, the use of this technique should be reconsidered in cases of myoma with atypical clinical presentation or symptomatology. Patients must be informed about the possibility of a nonidentified sarcoma and the possible impact on prognosis resulting from its morcellation.

Biological and pathological features in pregnancy-associated breast cancer: a matched case-control study.

BACKGROUND: The prognosis for breast cancer has been considered to be worsened by the coexistence of pregnancy. However, to date, significant controversy still exists regarding the pathological tumor features and prognosis of patients diagnosed with pregnancy-associated breast cancer (PABC). The aim of the present study was to analyze the different prognostic factors and outcome in PABC subset versus a non-PABC control group matched for age and year of diagnosis. MATERIALS AND METHODS: A total of 56 PABC cases were diagnosed from 1990 to 2008, for whom 73 non-PABC patients were identified. Pathological characteristics, immunohistochemical fea- tures, and differences in overall and disease-free survival were compared between both groups. RESULTS: Compared to non-PABC controls, PABC patients presented more advanced disease (31% vs 13%, p = 0.024) and greater lymph node involvement (53% vs 34%, p = 0.034). Pathological and tumor features tended to present poorer prognostic factors in the PABC subset. Survival was poorer in the PABC patients (five-year DFS 68% in PABC vs 86% in non-PABC, p = 0.12). However, analysing survival adjusted for stage and age, the authors did not find significant differences between both groups. CONCLUSIONS: PABC patients tended to be diagnosed in advanced breast disease and presented tumors with adverse pathological prognostic factors. While the authors found a poorer outcome in PABC group, no significant differences were observed with stage-matched analysis. The present results may suggest that the poorer prognosis observed within PABC women could not be due to pregnancy itself, but with a delay in diagnosis and tumor subtype pathological features.

Hormone receptor and HER2 status: The only predictive factors of response to neoadjuvant chemotherapy in breast cancer.

We report our experience in neoadjuvant breast cancer chemotherapy in a single centre between 2000 and 2011. We looked for predictive factors for response to neoadjuvant chemotherapy in the present study. A total of 110 consecutive breast cancer patients were treated with neoadjuvant chemotherapy in our centre. Pathological response was achieved in 24 HR+/HER2- (38.7%), 25 HER2+ (67.6%) and five triple-negative (45.5%) (p = 0.02) patients. No statistically significant differences were found in pathological tumour response according to T stage. The multivariate analysis revealed tumour subtype was the only associated factor for pathological response, with HER2 + tumours the best responders, OR 3.9 (1.5-9.9): 5-year DFS was 40% HER2+/no response; 78% HER2+/response; 65% HR+/HER2-/no response; 82% HR+/HER2-/response; 25% triple-negative/no response and 100% triple-negative/response. HR and HER2 status were the only prognostic factors for pathological response. pCR was correlated with survival in all tumour subtypes.

Histological grade concordance between diagnostic core biopsy and corresponding surgical specimen in HR-positive/HER2-negative breast carcinoma.

BACKGROUND: The identification and validation of suitable predictive and prognostic factors are a challenge to improve the treatment scheme selection. Discordances in histological grade can be established between core biopsy and surgical specimens. This is important in HR-positive/HER2-negative subgroup where histological grade identifies patients at high risk and is a strong determinant for treatment scheme. METHODS: A total of 350 consecutive invasive breast carcinoma biopsies were assessed and compared with surgical specimens in Institut Curie, Paris, France. Clinical, radiological and pathological data were recorded. RESULTS: Histological grade concordance rate in the HR+/HER2- group was 75%. A grade underestimation was mainly due to mitotic index misgrading (23%). Large tumours (P<0.05), premenopausal patients (P=0.005) and non-ultrasound-guided biopsies (P=0.04) were risk factors for misgrading. The highest discordance was found in tumours that required chemotherapy (39%, P<0.05), and it was related to an underestimation of histological grade on core biopsies (94%). CONCLUSIONS: Histological grade in HR+/HER2- group is important to identify patients with poor prognosis and start a systemic therapy. Histological grade discordance was correlated with an underestimation of mitotic index and factors probably associated with intratumor heterogeneity (premenopausal status, tumour size and the type of core biopsy performed). But such discordance did not appear to modify the therapeutic decision, because systemic treatment decision-making also integrates other variables. Determining histological grade in core biopsy can be especially important in HR-positive/HER2-negative subgroup where it identifies patients at high risk and is a strong determinant of the treatment scheme.

Role of lymphadenectomy in endometrioid endometrial cancer.

OBJECTIVE: To assess the risk factors associated with node involvement. STUDY DESIGN: In the period 1990-2008 a total of 265 endometrial cancers were treated in the Institut Universitari Dexeus. We analysed the rate of myometrial invasion, tumour grade, histological type and node involvement. RESULTS: Overall, 86% of tumours were endometrioid, 5.3% papillary serous, 4.9% mixed and 2.6% endometrial stroma sarcoma. Among those with endometrioid histology, lymphadenectomy was not performed (NL) in 85 cases (37.2%), whereas pelvic lymphadenectomy (PL) or pelvic and aortic lymphadenectomy (PAL) was carried out in 84 (36.84%) and 59 patients (25.87%), respectively. In NL patients the overall disease-free survival (DFS) rate at five years was 92.8%. In the PL group, node involvement was observed in 2.4% of cases and the five-year DFS rate was 92.3%. Among PAL patients, 18.6% showed node involvement (72.7% positive pelvic nodes and 63.6% aortic). Aortic involvement was present in 5.9% of cases when there was no pelvic disease, whereas in the presence of positive pelvic nodes the rate of aortic involvement was 50%. The DFS rate at five years was 93.6%. Referring to the risk factors, when infiltration was > 50% of the myometrium, lymph node involvement occurred in 37% of cases and G3 tumors in 45.5%. CONCLUSIONS: Node involvement is more commonly observed in cases with > 50% myometrial invasion and G3, accounting for 25% of cases that can be considered as at-risk patients. When node involvement is present it is equally distributed between the pelvic and aortic levels. As node involvement is a predictive factor for distant metastasis, the 25% of patients considered to be at risk should undergo pelvic and aortic lymphadenectomy

Neurofibroma of the vaginal wall.

BACKGROUND: Von Recklinghausen's disease is characterized by cutaneous manifestations but it is a systemic disease which may affect the genitourinary tract. CASE: A 20-year-old woman with a history of type-1 neurofibromatosis attended our center due to a vaginal nodule. Surgical treatment consisted of an incisional biopsy of the nodule. The anatomopathological diagnosis was plexiform neurofibroma. CONCLUSION: Periodical check-ups are recommended in asymptomatic vaginal neurofibroma whereas its radical excision should be avoided as such surgery is highly aggressive.

Prenatal ultrasound diagnosis of vasa praevia and analysis of risk factors.

OBJECTIVE: To evaluate the role of ultrasound in prenatal diagnosis of vasa praevia (VP) and to asses the risk of VP associated with different causal factors. MATERIAL AND METHODS: A retrospective study of the incidence of VP in a series of 12,063 deliveries between January 2000 and March 2005. We also studied the factors that predisposed for VP and the perinatal outcome of pregnancies. RESULTS: The prevalence of VP in our centre during this period was 0.07% (9 cases). All cases were prenatally diagnosed. The mean gestational age at diagnosis was 26 weeks. Multivariate analysis revealed the following associated factors: IVF pregnancies, bilobate or succenturiate placenta, and second-trimester placenta praevia, with an odds ratio of 7.75, 22.11 and 22.86, respectively. CONCLUSIONS: In our series, the prenatal diagnosis of all cases of VP achieved during the second-trimester scan allowed us to avoid any prenatal death related to this condition.