Fatima Laki

Validation and Limitations of Use of a Breast Cancer Nomogram Predicting the Likelihood of Non–Sentinel Node Involvement After Positive Sentinel Node Biopsy

BackgroundAxillary lymph node dissection (ALND) for patients with positive sentinel lymph nodes (SLNs) is currently under discussion in the literature. The breast cancer nomogram (BCN), an online tool developed by the Memorial Sloan-Kettering Cancer Center (MSKCC), aims to predict the risk of positive non-SLN in SLN-positive patients. The purpose of this study was to test the accuracy of the nomogram on patients with macrometastatic and micrometastatic SLN-positive biopsy findings.MethodsPatient characteristics, tumor pathology, and positive SLN characteristics were collected on 588 consecutive patients who underwent completion ALND. The MSKCC BCN tool was used to calculate risk of metastases for all 588 cases that included a subgroup of the 213 patients with SLN micrometastases. The BCN was performed for positive SLN biopsy findings regardless of the method of metastasis detection. Evaluation of the BCN was performed by the area under the curve method.ResultsThe BCN applied to all 588 patients achieved an area under the receiver operating characteristic curve (ROC) of .724 (range, .677–.771) compared with .76 in the MSKCC study. When the tool was applied solely to micrometastases found by hematoxylin and eosin staining and metastases found by immunohistochemistry, the area under the ROC was .538 (range, .423–.653).ConclusionsThe MSKCC nomogram has been validated for all the patients having a metastatic SLN at the Institut Curie. However, this model was not reliably predictive for positive non–SLN in cases with micrometastic positive SLN.

Breast-Conserving Treatment in the Elderly: Long-Term Results of Adjuvant Hypofractionated and Normofractionated Radiotherapy

PURPOSE To evaluate the long-term cause-specific survival (CSS), locoregional recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly breast cancer patients receiving adjuvant normofractionated (NF) or hypofractionated (HF) radiotherapy (RT). METHODS AND MATERIALS Between 1995 and 1999, 367 women aged >or=70 years with nonmetastatic Stage T1 or T2 tumors were treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They underwent wide tumor excision with or without lymph node dissection followed by RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy (25 fractions, 5 fractions weekly) to the whole breast, followed by a boost to the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The HF-RT schedule was indicated for the more elderly patients. RESULTS A total of 317 patients were in the NF-RT group, with 50 in the HF-RT group. The median follow-up was 93 months (range, 9-140). The 5- and 7-year CSS, LRFS, and MFS rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and 95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7-year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92% and 93% for MFS, respectively. CONCLUSION According to the findings from this retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for elderly patients. However, large-scale prospective randomized trials are needed to confirm these results.

How to Boost the Breast Tumor Bed? A Multidisciplinary Approach in Eight Steps

PURPOSE To describe a new procedure for breast radiotherapy that will improve tumor bed localization and radiotherapy treatment using a multidisciplinary approach. PATIENTS AND METHODS This pilot study was conducted by departments of radiation oncology, surgery, and radiology. A new procedure has been implemented, summarized as eight steps: from pre-surgery contrast CT to surgery, tumor bed planning target volume (PTV) determination, and finally breast and tumor bed irradiation. RESULTS Twenty patients presenting with T1N0M0 tumors were enrolled in the study. All patients underwent lumpectomy with the placement of surgical clips in the tumor bed region. During surgery, 1 to 5 clips were placed in the lumpectomy cavity before the plastic procedure. All patients underwent pre- and postoperative CT scans in the treatment position. The two sets of images were registered with a match-point registration. All volumes were contoured and the results evaluated. The PTV included the clips region, the gross tumor volume, and the surgical scar, with an overall margin of 5-10 mm in all directions, corresponding to localization and setup uncertainties. For each patient the boost PTV was discussed and compared with our standard forward-planned PTV. CONCLUSIONS We demonstrate the feasibility of a tumor bed localization and treatment procedure that seems adaptable to routine practice. Our study shows the advantages of a multidisciplinary approach for tumor bed localization and treatment. The use of more than 1 clip associated with pre- to postoperative CT image registration allows better definition of the PTV boost volume.

IMPROVING THE DEFINITION OF TUMOR BED BOOST WITH THE USE OF SURGICAL CLIPS AND IMAGE REGISTRATION IN BREAST CANCER PATIENTS

PURPOSE To evaluate the accuracy of a boost technique. METHODS AND MATERIALS Twenty-two patients underwent tumorectomy with placement of two or more clips in the surgical cavity before breast remodeling. Preoperative and postoperative computed tomography scans, with match-point registration, were performed on all patients. The relationship between the location of the gross tumor volume (GTV), defined on the preoperative scan, and clip clinical target volume (CTV) (clips with a 5-mm margin on the postoperative scan) was then studied, by use of commercial volume analysis software. RESULTS Of the patients, 4 had two clips, 2 had three clips, 8 had four clips, and 8 had five clips. The median GTV was 1.06 mL (range, 0.2-5.3 mL); clip CTV ranged from 2.4 to 21.5 mL. Volumetric analysis showed that in 7 cases (32%), there was no intersection between the GTV and the clip CTV, with the following distribution: 4 patients with two clips, 1 patient with three clips, 1 patient with four clips, and 1 patient with five clips. The common contoured volume was defined as the percent ratio between the intersection of the GTV and clip CTV and the GTV. It was found to be significantly increased if three or more clips were used vs. only two clips (common contoured volume, 35.45% vs. 0.73%; p = 0.028). Finally, the GTV and clip CTV volume relationship can be presented as follows: 12.5% to 33% overlap in 8 patients (36.4%), 50% to 75% in 5 patients (22.7%), and greater than 90% in 2 patients (9%). CONCLUSIONS The use of three or more clips during tumorectomy increases the accuracy of tumor bed delineation.

Prophylactic salpingo-oophorectomy in a series of 89 women carrying a BRCA1 or a BRCA2 mutation†

Prophylactic salpingo‐oophorectomy (SO), which is recommended in BRCA1/2 mutation carriers, still needs to be reappraised.

Long-Term Prognostic Performance of Ki67 Rate in Early Stage, pT1-pT2, pN0, Invasive Breast Carcinoma

Background Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1–pT2, pN0) breast cancer patients. Methods 456 patients treated in 1995–1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed. Results All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5–191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (>20%) Ki67 rate [HR = 3 (1.8–4.8), p<10e−06] and HG3 [HR = 4.4 (2.2–8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5–4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01–4.8), p = 0.04]. Conclusions We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1–pT2, pN0, breast cancers.

Reasons of not having breast reconstruction: a historical cohort of 1937 breast cancer patients undergoing mastectomy.

BackgroundThe aims of the study were to investigate the factors associated with not having breast reconstruction following mastectomy and to assess patient satisfaction with information on reconstruction.Patients and methodsWe analysed a historical cohort of 1937 consecutive patients who underwent mastectomy at Institut Curie between January 2004 and February 2007. Their sociodemographic and clinicobiological characteristics were recorded in a prospective database. A questionnaire was sent to 10% of nonreconstructed patients.ResultsThe proportion of patients with invasive cancer was 82.7%. The rate of nonreconstruction in patients with in situ and invasive cancer was 34.6% and 74.9%, respectively. On multivariate analysis, only employment outside the home was associated with reconstruction in patients with in situ cancer (p < 0.001). In patients with invasive cancer, employment status (p < 0.001) and smoking (p = 0.045) were associated with reconstruction, while age > 50, ASA score >1, radiotherapy (p < 0.0001) and metastatic status (p = 0.018) were associated with nonreconstruction. For 80% of questionnaire responders, nonreconstruction was a personal choice, mainly for the following reasons: refusal of further surgery, acceptance of body asymmetry, risk of complications and advanced age. Information on reconstruction was entirely unsatisfactory or inadequate for 62% of patients.ConclusionBetter understanding the factors that influence decision of nonreconstruction can help us adapt the information to serve the patient’s personal needs.

Extensive pure ductal carcinoma in situ of the breast: Identification of predictors of associated infiltrating carcinoma and lymph node metastasis before immediate reconstructive surgery

AIM To identify predictors for infiltrating carcinoma and lymph node involvement, before immediate breast reconstructive surgery, in patients with an initial diagnosis of extensive pure ductal carcinoma in situ of the breast (DCIS). PATIENTS AND METHODS Between January 2000 and December 2009, 241 patients with pure extensive DCIS in preoperative biopsy had underwent mastectomy. Axillary staging (sentinel node and/or axillary dissection) was performed in 92% (n = 221) of patients. Patients with micro-invasive lesions at initial diagnosis, recurrence or contralateral breast cancer were excluded. RESULTS Respectively 14% and 21% of patients had a final diagnosis of micro-invasive carcinoma (MIC) and invasive ductal carcinoma (IDC). Univariate analysis showed that the following variables at diagnosis were significantly correlated with the presence of either MIC or IDC in the mastectomy specimen: palpable tumor (p = 0.002), high grade DCIS (p = 0.002) and detection of an opacity by mammography (p = 0.019). Axillary lymph node (ALN) involvement was reported in 9% of patients. Univariate analysis suggested that a body mass index higher than 25 (p = 0.007), a palpable tumor (p = 0.012) and the detection of an opacity by mammography (p = 0.044) were associated with an increased rate of ALN involvement. CONCLUSION Skin-sparing mastectomy and immediate breast reconstruction (IBRS) has become increasingly popular, especially for patients with extended DCIS of the breast. This study confirmed that extended DCIS is associated with a substantial risk of finding MIC or IDC on the surgical specimen but also ALN involvement. Adjuvant systemic treatment and/or radiotherapy could be indicated for some of these patients after the surgery. Patients should be informed of the rate of 1) complications associated to IBRS that will potentially delay the introduction of systemic or local therapy 2) complications associated to radiotherapy after IBRS.

Réseaux lymphatiques de la glande mammaire : l’identification du ganglion sentinelle revue à la lumière des anciens anatomistes

Lymphatic drainage of the mammary gland. Sentinel node biopsy revisited at the light of historical anatomical works Sentinel node biopsy for breast cancer was described in 1994 and is part of the daily treatment of small operable breast cancers. Colorimetric and/or isotopic technique allows identification of breast lymphatic network and its drainage towards the axilla. Periareolar or peri-tumoral injection of the Isotope or patent blue were demonstrated as injecting the same axillary node or group of nodes. The anatomy of the breast lymphatic drainage was described in the 19th century and before Sappey’s description one can say that the aesthetical and lactation diseases were the main concerns about the breast. Even though Queen Anne d’Autriche was treated with red iron for her T IV, the treatment of breast cancer remained poorly described until the end of the 19th century. Screening programs allow the discovery of smaller and smaller cancers in which the classical axillary dissection is no more useful. Identification of breast lymphatic drainage rediscovered the ancients’ anatomical works with lymphotropic dye and isotopes which can be used in vivo. The re-discovery of the anatomy by these authors is very valuable and very useful for our patients

Scleroderma and radiotherapy as part of the treatment of breast carcinoma: Six cases and a short critical review of the literature

Purpose : To add six new cases to the literature and to determine whether women with pre-existing scleroderma have an increased incidence of complications after breast-conserving therapy. Methods and Materials : From 1995 to 2005, nine patients with pre-existing scleroderma were treated for their breast cancer at the Institute Curie. Six of them underwent radiotherapy. The patients who underwent radiotherapy were irradiated using high-energy photons of a cobalt unit and/or linear accelerator, either before or after surgery, or were exclusively treated using radiation therapy. The early and late skin reactions have been evaluated using the Acute Radiation Morbidity Scoring Criteria (RTOG) and Late Radiation Morbidity Scoring Scheme (RTOG, EORTC). Results : Median follow-up of the six irradiated patients was 34 months (range from 10 to 120 months). Early reactions were as follows: grade 1 in two cases, grade 2 in two cases, and grade 3 in two cases. Late toxicity was as follows: grade 0 in three patients, currently at 56, 48, and 12 months of follow-up; grade 1, slight atrophy, in two patients; grade 3 reaction with marked atrophy in one patient, followed up for 120 months now. There was no toxicity worse than grade 3 in these series. Conclusions : This small study cannot provide evidence that scleroderma increases the risk of developing early and late toxicity. Patients with scleroderma must be discussed in multidisciplinary meetings to adapt their treatment to their rheumatologic history. When radiotherapy is considered, more attention must be paid to the protection of normal tissues. Careful follow-up during and after the radiation therapy remains of paramount importance in this specific population of patients.