Factors Involved in Delaying Initiation of Adjuvant Chemotherapy After Breast Cancer Surgery.

BACKGROUND: Delays in initiating adjuvant chemotherapy after breast cancer surgery seems to have an impact on patients' risk of relapse and their survival rate. The aim of this retrospective study was to identify factors delaying initiation of adjuvant chemotherapy after breast surgery. MATERIAL AND METHODS: All patients undergoing surgical treatment for mammary cancer between June 2014 and June 2015 and receiving adjuvant chemotherapy were selected retrospectively. RESULTS: In multivariate analysis, 3 factors significantly delay initiation of adjuvant chemotherapy: a secondary procedure (odds ratio [OR], 6.67; P = .00012), inclusion in a therapeutic trial (OR, 8.46; P = .0013), and a positive HER2 status (OR, 3.02; P = .063 [statistically significant]). DISCUSSION: This study provides a brief overview of the population most likely to experience a delay in the initiation of their adjuvant chemotherapy after cancer surgery. Our findings should assist interventions during initial management.

[Techniques and complications of non-genetic risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)]. / Modalités et morbidité des mastectomies de réduction de risque en dehors du risque avéré de prédisposition héréditaire : recommandations du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: Based on an updated review of the international literature covering the different surgical techniques and complications of risk reducing mastectomies (RRM) in non-genetic context, the Commission of Senology (CS) of the College National des Gynécologues Obstétriciens Français (CNGOF) aimed to establish recommendations on the techniques to be chosen and their implementation. DESIGN: The CNGOF CS, composed of 24 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The CS adhered to and followed the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted. METHODS: The CS considered 6 questions in 4 thematic areas, focusing on oncologic safety, risk of complications, aesthetic satisfaction and psychological impact, and preoperative modalities. RESULTS: The application of the GRADE method resulted in 7 recommendations, 6 with a high level of evidence (GRADE 1±) and 1 with a low level of evidence (GRADE 2±). CONCLUSION: There was significant agreement among the CS members on recommendations for preferred surgical techniques and practical implementation.

[Impact of omission of axillary dissection on adjuvant therapy in patients with metastatic sentinel lymph nodes according to the ACOSOG Z0011 criteria]. / Impact de l'omission du curage axillaire sur les traitements adjuvants chez les patientes ayant un ganglion sentinelle métastatique et répondant aux critères d'inclusion de l'ACOSOG Z0011.

OBJECTIVES: The results of the ACOSOG Z0011 questioned the usefulness of axillary lymph node dissection (ALND) in case of metastatic sentinel lymph node (SLN). The aim of our study was to assess the impact of the omission of ALND according to the inclusion criteria of the ACOSOG Z0011 study if SLN are metastatic but also the consequences on prescription of the application of a new standard of care for adjuvant treatment. PATIENTS AND METHODS: This retrospective study included, between November 2007 and January 2012, patients with T1-T2N0 breast cancer and metastatic SLN meeting the criteria for omission of completion ALND according to the study of the ACOSOG Z0011. Patients were submitted anonymously and randomly in multidisciplinary meeting (MM) 3 times: with complete information including ALND (MM1), with information from SLN alone (MM2) and with complete information of ALND according to the current protocols in 2013 (MM3). During each presentation, we collected the decision of the different adjuvant treatments proposed: chemotherapy, hormonal therapy, radiotherapy (with radiation fields). Then, we compared therapeutic proposals of the 3 presentations. RESULTS: Fifty-eight patients were eligible for inclusion criteria of the ACOSOG Z0011. Treatments actually proposed during MM1 consisted of 94.8 % of chemotherapy, 77.6 % of breast and lymph nodes radiotherapy and 91.4 % of hormone therapy. During the MM2, there was no significant difference compared to the decision taken during MM1. In fact, during MM2, we decided chemotherapy, radiotherapy and hormonotherapy respectively in 89.7, 79.3 and 91.4 % of the cases. During the MM3, it was shown a significant decrease in the indications of chemotherapy (82.8 %, P=0.03) and lymph nodes irradiation (56.9 %, P=0.02) compared to the therapeutic proposals of the MM1. DISCUSSION AND CONCLUSION: The lack of information of ALND does not seem to significantly alter indications for adjuvant treatment. Otherwise, the evolution of our references causes a decrease in adjuvant therapy.

Evaluation and impact of residual disease in locally advanced cervical cancer after concurrent chemoradiation therapy: results of a multicenter study.

BACKGROUND: The aim of this study was to evaluate the diagnosis and impact of residual disease (RD) after concurrent chemoradiation therapy (CRT) in locally advanced cervical cancer (FIGO IB2-IVA). METHODS: This retrospective multicenter study included 159 patients who were treated with completion surgery after CRT between 2006 and 2012. Magnetic resonance imaging (MRI) was performed 4-6 weeks after CRT and compared to pathological evidence of residual disease. Kaplan-Meier survival curves were plotted and univariate/multivariate analyses were performed to assess the association between RD and the outcome. RESULTS: Residual disease was present in 45.3% of the patients and detected by MRI in 57.1%. The MRI had a 29.2% false positive rate and an 11.1% false negative rate. The overall survival (OS) rates at 3 and 5 years were 78.6% (CI 95% [71%-86.9%]) and 76.5% (CI 95% [68.2%-85.7%]), respectively. The disease free survival (DFS) rates at 3 and 5 years were 73.4% (CI 95% [65.6%-82%]) and 71.1% (CI 95% [62.7%-80.1%]), respectively. RD greater than 10 mm decreased DFS (HR = 4.84, p = 0.03), whereas RD between 1 and 10 mm (HR = 0.31, p = 0.58) and less than 1 mm (HR = 0.37, p = 0.54) had no impact on DFS. The OS was not changed by RD. DISCUSSION: The MRI accuracy value is not sufficient to select patients who might benefit from completion surgery. Residual disease over 10 mm decreased DFS but did not impact OS.

Systematic cavity shaving: modifications of breast cancer management and long-term local recurrence, a multicentre study.

BACKGROUND: The status of the surgical margins of lumpectomy is one of the most important determinants of local recurrence in breast cancer. Systematically practicing cavity margin resection is debated but may avoid surgical re-excision and allow the diagnosis of multifocality. METHODS: This multicentric retrospective study included 294 patients who underwent conservative management of breast cancer with 2-4 systematic cavity shavings. Clinico-biological characteristics of the patients were collected in order to establish whether surgical management was modified by systematic cavity shaving. Local recurrence rate with a long-term follow up of minimum 4 years was evaluated. RESULTS: Cavity shaving avoided the need for re-excision in 25% of cases and helped in the diagnosis of multifocality in 8% of cases. Resection volume was not associated with usefulness of the cavity shaving. No predictive factor of positive cavity shaving was found. The rate of local recurrence was 3.7% and appeared in a median time of 3 years and 8 month. Only one quarter of the patients with local recurrence had initially positive lumpectomy margins but negative cavity shaving. DISCUSSION: Systematic cavity shaving can change surgical management of conservative treatment. No specific target population for useful cavity shaving was found, such that we recommend utilising it systematically.

Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas.

BACKGROUND: The aim of this study was to compare clinical and pathological outcomes after neoadjuvant chemotherapy between oestrogen receptor (ER)-positive invasive pure lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). METHODS: This analysis included 1895 patients (n=177 ILC; n=1718 IDC), with stage I-III breast cancer, who received neoadjuvant chemotherapy. Clinical and pathological response rates, the frequency of positive surgical margins and rate of breast-conserving surgery were compared. RESULTS: There was a trend for fewer good clinical responses in ILC compared with IDC. Tumour downstaging was significantly less frequent in ILC. Positive or close surgical resection margins were more frequent in ILC, and breast-conserving surgery was less common (P<0.001). These outcome differences remained significant in multivariate analysis, including tumour size, nodal status, age, grade and type of chemotherapy. Invasive pure lobular carcinoma was also associated with a significantly lower pathological complete response (pCR) rate in univariate analysis, but this was no longer significant after adjusting for tumour size and grade. CONCLUSION: Neoadjuvant chemotherapy results in lower rates of clinical benefit, including less downstaging, more positive margins and fewer breast-conserving surgeries in ER-positive ILC compared with ER-positive IDC. Pathological complete responses are rare in both groups, but do not significantly differ after adjusting for other variables.

[Quality of life after laparoscopic radical hysterectomy for cervical cancer: study of 22 cases]. / Colpohystérectomie élargie par voie cœlioscopique dans les cancers du col utérin : étude de qualité de vie. À propos de 22 cas.

OBJECTIVE: Laparoscopic radical hysterectomy is currently the surgical treatment of cervical cancer. The objective of this study was to evaluate the quality of life of patients with cervical cancer treated by radical hysterectomy by laparoscopy. PATIENTS AND METHODS: Quality of life was evaluated in 22 patients with cervical cancer (FIGO stade IB1-IIB) treated by laparoscopic radical hysterectomy. The study employed two types of survey questionnaires: EORTC QLQ-C 30 and QLQ-OV 28. RESULTS: After a median follow-up of 25 months (range: 12-48 months), the average global health scores and quality of life after the surgery was high, indicating a good overall quality of life. The symptoms most commonly implicated were fatigue and insomnia. The average symptom scores (abdominal, peripheral neuropathy, side effects of chemotherapy) was low, meaning little inconvenience. It noted, however, an exception for the symptoms of menopause that generate significant discomfort in several patients. Among patients with a regular sexual activity, most described a change in frequency and quality of reporting. DISCUSSION AND CONCLUSIONS: Patients with cervical cancer treated by laparoscopy have good overall quality of life. The function that is most affected by the treatment in the majority of patients is sexual function. A comparative prospective study with laparotomy would be necessary.

Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer.

We examined whether baseline Ki67 expression in estrogen receptor-positive (ER+) primary breast cancer correlates with clinical benefit and time to progression on first-line endocrine therapy and survival in metastatic disease. Ki67 values and outcome information were retrieved from a prospectively maintained clinical database and validated against the medical records; 241 patients with metastatic breast cancer were included--who had ER+ primary cancer with known Ki67 expression level--and received first-line endocrine therapy for metastatic disease. Patients were assigned to low (<10 %), intermediate (10-25 %), or high (>25 %) Ki67 expression groups. Kaplan-Meier survival curves were plotted and multivariate analysis was performed to assess association between clinical and immunohistochemical variables and outcome. The clinical benefit rates were 81, 65, and 55 % in the low (n = 32), intermediate (n = 103), and high (n = 106) Ki67 expression groups (P = 0.001). The median times to progression on first-line endocrine therapy were 20.3 (95 % CI, 17.5-38.5), 10.8 (95 % CI, 8.9-18.8), and 8 (95 % CI, 6.1-11.1) months, respectively (P = 0.0002). The median survival times after diagnosis of metastatic disease were also longer for the low/intermediate compared to the high Ki67 group, 52 versus 30 months (P < 0.0001). In multivariate analysis, high Ki67 expression in the primary tumor remained an independent adverse prognostic factor in metastatic disease (P = 0.001). Low Ki67 expression in the primary tumor is associated with higher clinical benefit and longer time to progression on first-line endocrine therapy and longer survival after metastatic recurrence.

[Sentinel lymph node detection in patients with early-stage breast cancer: which site of injection in 2011?]. / Détection du ganglion sentinelle chez les patientes atteintes d'un cancer du sein à un stade précoce : quel site d'injection en 2011 ?

Sentinel lymph node (SLN) mapping and biopsy have emerged as the technique of choice for axillary staging of breast cancer. Several methods have been developed to identify SLNs, including peritumoral or periareolar injection of blue dye or technetium colloid. The optimal site for injection of mapping tracers is controversial in SLN. The peritumoral injection provides information on the deep lymphatic drainage and the internal mammary chain. The advantages of periareolar injection are simplicity, the ability to perform it in non-palpable tumors, and the potential enhancement of uptake via the subareolar lymphatic plexus. The results of multiinstitutional study have indicated that superficial injection (periareolar or peritumoral) is associated with a better identification rate and an equal false-negative rate compared to deep peritumoral (PT) injection. However, the false-negative rate of periareolar injection has not been formally demonstrated.

[Sentinel node biopsy after multiple breast and axillary surgeries]. / Biopsie du ganglion sentinelle après chirurgies multiples du sein et du creux axillaire.

Sentinel node (SN) biopsy is considered as a standard of care in the staging of breast cancer. We report SN biopsy in a rare case of second ipsilateral subcutaneous recurrence in patient with previous left breast cancer initially treated by breast radiotherapy followed by mammectomy with axillary dissection and multiple mammoplasty. Lymphoscintigraphy was performed. Two axillary radioactive SNs were identified and removed without lymph node involvement at final histology. To conclude, re-operative axillary dissection by SN biopsy after previous axillary and breast surgeries is technically feasible.

[Lymph node surgical staging for locally advanced cervical cancer]. / Stadification ganglionnaire des cancers du col utérin avancé

Lymph node staging in patients with locally advanced cervical cancer is the most important prognostic factor and also leads to adjuvant treatment choice. Because of the lymphadenectomy associated morbidity and delay in the beginning of adjuvant therapy, noninvasive approaches were developed during the last decennia. Recently, positron emission tomography employing a glucose analogue (FDG-PET) has been shown to be more sensitive and more specific than magnetic resonance imaging or than computed tomography usually used in diagnosis of pelvic and para-aortic lymph node metastases. Even if recent studies have reported promising results, surgical pelvic and para-aortic staging remains actually the most accurate procedure for evaluating lymph node metastases. This procedure should be accomplished by transperitoneal or extraperitoneal laparoscopy, with the benefits of minimal morbidity, shorter length of hospital stay and no significant increase of complications comparing to laparotomy approach. Laparoscopy also allows an early start of adjuvant treatment, this delay constituting an important prognostic factor for patients with locally advanced cancer. However, the survival benefit of lymph node dissection is still controversial and should be proved in randomised studies.

[Is there an interest in para-aortic lymphadenectomy in operable endometrial cancer?]. / Y a-t-il un intérêt au curage lomboaortique dans les cancers de l'endomètre opérables ?

The indication and extent of lymph node dissection in the surgical management of endometrial cancer remains controversial especially concerning the para-aortic lymph nodes. The therapeutic benefit of the lymph node dissection is criticized mainly for low-risk patients for extra-uterine spread. Surgically staging patients is the best method to predict node involvement and it allows an optimal decision for adjuvant therapy to be taken. The different prognostic factors for para-aortic lymph nodes metastasis are histological grade and size of the tumour, myometrial wall invasion and lymphovascular dissemination, as well as positive pelvic lymph nodes. However, these elements are not correctly evaluated before and during the surgery. Positive para-aortic lymph nodes can be found without a lymphatic spread to the pelvic area. Even though the prevalence of para-aortic node involvement is weak, it seems legitimate to propose in selected cases of important lymph node involvement, it's complete dissection if a pelvic lymphadenectomy is indicated and if it is surgically possible.

[Atypical ductal and lobular hyperplasia of the breast]. / Hyperplasies atypiques du sein.

Atypical hyperplasia represents 4% of all benign breast diseases. There are two different types: atypical ductal hyperplasia and atypical lobular hyperplasia. Aside columnar cell lesion. They represent an early stage of some forms of low grade carcinoma in situ and invasive carcinomas. Atypical hyperplasia is a benign lesion with intermediate carcinologic risk and the existence of a concomitant aggressive lesion should be suspected. When atypical lesion is found on a biopsy specimen, surgical excision is recommended especially in case of atypical ductal hyperplasia. A regular supervision is recommended.

[Role of sentinel node biopsy in early-stage cervical cancer in the therapeutic strategy]. / Place du ganglion sentinelle dans la stratégie thérapeutique du cancer du col de l'utérus aux stades précoces.

Early-stage cervical cancer (IA2 and IB1) treatment consists in surgery with a radical colpohysterectomy associated to a systematic pelvic lymphadenectomy more or less a paraaortic lymphadenectomy (Wertheim-Meigs surgery). Pelvic lymph node involvement is the main independent prognostic factor and justifies an adjuvant therapy. Sentinel lymph node (SLN) procedure allows a reliable evaluation of the lymph node status thanks to an accurate histologic analysis. This procedure is still not validated in practice, which means the bilateral pelvic lymphadenectomy is systematically done whatever the lymph node status is. Nevertheless the purpose of the SLN biopsy in cervical cancer does not consist in avoiding an unnecessary lymphadenectomy, which is not really associated with a major morbidity. Actually, a better initial stadification would allow to fit to the risk of recurrence not only the radicality of the surgery, but also the adjuvant therapy. The morbidity of a radical surgery could be limited for good prognosis patients and avoided for the benefit of a concomitant chemoradiotherapy.

[Models to predict non sentinel lymph node status in breast cancer patients with metastatic sentinel lymph node]. / Modèles prédictifs d'envahissement des ganglions non sentinelles en cas de métastases des ganglions sentinelles dans le cancer du sein.

In breast cancer, nine models have been developed to predict non SN status in patients with SN metastasis. Four models are nomograms: the Memorial Sloan-Kettering Cancer Center nomogram (MSKCC nomogram), the nomogram of Degnim et al. (Mayo nomogram), the nomogram of Pal et al. (Cambridge nomogram), and the nomogram of Kohrt et al. (Stanford nomogram). Three models are scoring systems: the Tenon score, the score from the M.D. Anderson Cancer Center (MDA score), and the score of Saidi et al. Finally, two are recursive partitioning tools developed by Kohrt et al. Before being used in routine, these models have to be validated in independent populations based on discrimination and calibration. However, the main issue is their clinical utility based not only on the low false negative rate but also its potential to discriminate patients with a low risk of non SN involvement. Several institutions have tested the MSKCC nomogram, with AUC ranging from 0.58 to 0.86. It was not validated by four studies which did not recommend its use even in patients with micrometastasis.The external validation of the Tenon score confirmed its relevance with an AUC of 0.82.