Outcomes of postoperative radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study in 752 patients.

OBJECTIVES: The aim of this study was to assess efficacy, tolerability, and the impact of comorbidities on outcomes in older women treated by radiation therapy (RT) for non-metastatic breast cancer. MATERIALS AND METHODS: Women aged ≥70 years at diagnosis who received postoperative RT for primary non-metastatic BC between 2003 and 2009 were retrieved from the Institut Curie registry. We calculated the Charlson Comorbidity Index (CCI) for each patient. We analyzed overall survival (OS), progression free survival (PFS), and acute and late toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. RESULTS: A total of 752 patients were included in this study. Median age at diagnosis was 75 years [70-93.3]. With a median follow-up of 7.3 years [0.4-12.9], OS and PFS at 5 years were 87.2% CI95%[84.8-89.8] and 85.7% CI95%[83.1-88.3], respectively. OS at 5 years was statistically different according to the CCI: 90.7% CI95%[87.6-93.9] for a CCI of 0, 85.8% CI95%[81.8-90.1] for a CCI of 1, and 79.1% CI95%[71.1-87.9] for a CCI ≥ 2 (p < 0.01, log-rank test), respectively. Similar results were found for PFS (p < 0.05, log-rank test). Most (23.3%) of the patients had no toxicities; of those who experienced side-effects, the majority were grade I or II (96.9%). CONCLUSION: Postoperative RT for non-metastatic BC in older women is effective and well-tolerated. Outcome is impacted by age and comorbidities, which are clear independent prognostic factors.

Whole breast radiotherapy in the lateral isocentric lateral decubitus position: Long-term efficacy and toxicity results.

PURPOSE: To evaluate previously published whole breast radiotherapy (WBRT) using ILD (isocentring lateral decubitus) technique in terms of toxicity and efficacy. MATERIALS AND METHODS: From 2006 to 2010, 832 female patients with early-stage breast cancer (BC) treated by conservative surgery underwent 3D-conformal WBRT-ILD at Institut Curie. The acute toxicity of treatment was evaluated weekly and the late toxicity (6months and later after the treatment) was evaluated every 6months till the 5th year after the end of the radiotherapy using NCI CTC v3.0 scale. Dosimetric study was performed to analyse the mean cardiac dose and the mean homolateral and contralateral lung doses. RESULTS: The median follow up was 6.4years. The median age was 61.5years (range, 29-90), and median body mass index (BMI) was 26.3. Fifty one percent of the patients presented left sided BC and 49% right sided. Different type of fractions were used: 46.5% of pts.: 50 (breast)+16Gy (boost) in 33fractions (fr), in 17.9%-50Gy/25fr, in 26.1%-40/15fr or 41.6Gy/13fr and in 9.5%: 30Gy/5fr. Acute dermatitis was present in 93% with a median of apparition of 4weeks, and only 2,8% grade 3. In multivariate analysis, the cup size had significant influence (p=0.0004) and the fractionation had a significative influence (p=0.0001). In the all patients' population, 94.1% of cases had no skin toxicity at 1year. No cardiac or pulmonary toxicity was reported. The median overall survival had not been reached at the end of follow-up. We observed 36 (3.6%) recurrences, as following: 30 local (breast) recurrences, 4 lymph node (LN), and 2pts experiencing both. CONCLUSION: Whole breast radiotherapy in the lateral decubitus position provides excellent results in terms of local control and survival. ILD is well tolerated with very good acute toxicity profile. No cardiac or pulmonary toxicity were observed in this study. Longer follow-up is needed to confirm these results.

Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection.

BACKGROUND: A better understanding of the molecular profile of anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognostic and predictive factors for response to treatment. METHODS: We retrospectively analysed tumours from ASCC patients for mutational analysis of KRAS, NRAS, HRAS, BRAF, PIK3CA, MET, TP53 and FBXW7 genes by HRM and Sanger sequencing analysis. RESULTS: Specimens from 148 patients were analysed: 96 treatment-naive tumours and 52 recurrences after initial radiotherapy (RT) or chemoradiotherapy (CRT). Mutations of KRAS, PIK3CA, FBXW7 and TP53 genes were present in 3 (2.0%), 30 (20.3%), 9 (6.1%) and 7 tumours (4.7%), respectively. The distribution of the mutations was similar between treatment-naive tumours and recurrences, except for TP53 mutations being more frequent in recurrences (P=0.0005). In patients treated with abdominoperineal resection (APR) after relapse (n=38, median follow-up of 18.2 years), overall survival (OS) was significantly correlated with HPV16 status (P=0.048), gender (P=0.045) and PIK3CA mutation (P=0.037). The PIK3CA status retained its prognostic significance in Cox multivariate regression analysis (P=0.025). CONCLUSIONS: Our study identified PIK3CA mutation as an independent prognostic factor in patients who underwent APR for ASCC recurrence, suggesting a potential benefit from adjuvant treatment and the evaluation of targeted therapies with PI3K/Akt/mTor inhibitors in PIK3CA-mutated patients.

[Sophrology for patients in oncology]. / La sophrologie à la rencontre des patients en oncologie.

It is important to support patients with cancer during their care pathway and even beyond. They undergo long and difficult treatments, all anxiety-causing situations and sources of stress. Sophrological techniques help patients to find calm, lessen their fears and offer them the opportunity to work on themselves through simple easily reproducible exercises. This observation has been verified by a study carried out at the Institut Curie with patients undergoing chemotherapy.

Pathological Characteristics of Both Tumors in Bifocal and Bicentric Breast Cancer.

AIM: The objective of the present study was to describe the biological characteristics of each lesion in patients with bifocal/bicentric (BF/BC) breast cancer. PATIENTS AND METHODS: We retrospectively reviewed the charts of 205 patients diagnosed with BF/BC cancer. The degree of concordance between the two lesions was assessed using Pearson product-moment correlation coefficients. RESULTS: A total of 205 patients were included. Both tumors displayed the same histological type in 182 patients (89%). The same grade was found for both tumors in 178 of the cases (96.7% and 100% for grade 3 lesions). Immunohistochemical concordance between the two tumors was excellent, with correlation coefficients of 0.98, 0.96 and 0.99 for estrogen receptors (ER), progesterone receptors (PR) and Ki67, respectively. Human Epidermal growth factor Receptor 2 (HER2) status was available for both tumors in 177 cases (86%), with a perfect concordance. We did not find any differences in molecular sub-type between tumor foci. CONCLUSION: Immunohistochemistry should be performed only on the main tumor in cases of BF/BC cancer.

Outcome of oncoplastic breast-conserving surgery following bracketing wire localization for large breast cancer.

PURPOSE: The purpose of this study was to evaluate the outcome of breast conserving surgery comparing oncoplastic surgery (OS) and standard lumpectomy (SL) after preoperative bracketing wire localization of large neoplastic lesions. METHODS: We retrospectively reviewed the medical records and the mammograms of patients operated on at the Institut Curie between May 2005 and September 2011 after bracketing wire localization under mammographic and/or sonographic guidance. RESULTS: 113 patients underwent surgery for a pre-operative diagnosis of DCIS (n = 80), micro-invasive carcinoma (n = 9) or invasive carcinoma (n = 24), by OS (n = 73) or SL (n = 40). In the OS group, radiological size (52 mm vs 39 mm, p < 0.001) and resection volumes (246 cc vs 88 cc, p < 0.00001) were significantly higher than in the SL group. Rates of clear histologic margins (60 vs 62%, NS), complete excision of microcalcifications (78% vs 72%, NS) and re-intervention rate (40% vs 42%, NS) were equivalent. The rate of local recurrence at 24 months was 3% [0-7.1] in patients with conservative treatment (n = 3). With a median follow-up of 40 months, 5 local relapses (two with axillary metastatic involvement), two distant metastatic evolution, one contralateral breast cancer and one death unrelated to cancer occurred. CONCLUSION: Following bracketing wire localization, OS allowed the conserving management of significantly larger lesions with wider resection volumes, without significant increase in margin involvement or re-intervention rate, and equivalent rate of microcalcifications clearance compared to SL.

A prospective, descriptive cohort study of malignant wound characteristics and wound care strategies in patients with breast cancer.

Few studies have addressed the effects of dressings on malignant wounds. A 20-month (May 2010 to January 2011) descriptive, prospective cohort study was conducted by the Wound Care Unit of Institute Curie, Paris, France to evaluate the use of various local care procedures and characteristics of malignant wounds. Symptoms and wound management methods were observed over a period of 42 days in 32 patients (all women, mean age 60 years, range 30-96 years, most with infiltrating ductal carcinoma). After cleansing (with either sterile saline or water), a variety of wound treatments were used based on specific wound characteristics, including calcium alginate, hydrocellular, interface, and active charcoal and superabsorbent dressings. Wound size, color (red, pink, black, yellow), periwound condition, surface wound organisms (number of species and quantity), and signs of infection, along with wound-related pain (rated on a verbal rating scale), odor, bleeding (spontaneous or induced), and exudate (rated on a four-level scale as none, slight, moderate, intense) were assessed at baseline and on days 21 and 42 of treatment. The degree to which each symptom was managed was scored as controlled, partly controlled, or not controlled. Mean initial wound size did not change over the evaluation period; most (74%) wounds were characterized as being inflamed. No infectious episodes were observed during the duration of the evaluation. Exudate and bleeding were generally controlled with hemostatic dressings, calcium alginate dressings, or absorbent pads. Odor was not completely controlled with charcoal dressing and was noted to be significantly greater in patients with >105/g bacterial counts and/or with one or more anaerobic bacteria (P = 0.05). At day 0, 13 out of 25 patients (50%) had uncontrolled pain; pain ratings did not change over the course of the study. Clinical research on specific clinical practice (eg, topical morphine for pain) and to assess the comparative efficacy of different care approaches on controlling the local symptoms of malignant wounds is warranted to improve the quality of care, which may affect patient quality of life.

[Breast cancer and the hand-foot syndrome]. / Cancer du sein et syndrome mains-pieds.

Regarding patients being treated for breast cancer and on oral capecitabine, the main side effect is the hand-foot syndrome (HFS), or Palmar-Plantar Erythrodysesthesia (PPE).). This could be inconvenient or even debilitating depending on the grade. The Day Care Centre at the Institut Curie in Paris (75) conducted a prospective study on patients treated with oral capecitabine for advanced breast cancer, to assess the rate of appearance of the hand-foot syndrome and the impact of paramedical follow-up on the occurrence of this side effect.

Breast and ovarian cancer risk management in a French cohort of 158 women carrying a BRCA1 or BRCA2 germline mutation: patient choices and outcome.

Description of the various modalities of breast and ovarian cancer risk management, patient choices and their outcome in a single-center cohort of 158 unaffected women carrying a BRCA1 or BRCA2 germline mutation. Between 1998 and 2009, 158 unaffected women carrying a BRCA1 or BRCA2 gene mutation were prospectively followed. The following variables were studied: general and gynecological characteristics, data concerning any prophylactic procedures, and data concerning the outcome of these patients. Median age at inclusion was 37 years and median follow-up was 54 months. Among the 156 women who received systematic information about prophylactic mastectomy, 5.3 % decided to undergo surgery within 36 months after disclosure of genetic results. Prophylactic salpingo-oophorectomy was performed in 68 women. Among women in whom follow-up started between the ages of 40 and 50 years, prophylactic salpingo-oophorectomy was performed, within 24 months after start of follow-up, in 83.7 and 52 % of women with BRCA1 and BRCA2 mutations, respectively. Twenty four women developed breast cancer. Ovarian cancer was detected during prophylactic salpingo-oophorectomy in two women (2.9 %). In this cohort of French women carrying BRCA1/2 mutations, prophylactic mastectomy was a rarely used option. However, good compliance with prophylactic salpingo-oophorectomy was observed. This study confirms the high breast cancer risk in these women.

Can we decrease the skin reaction in breast cancer patients using hyaluronic acid during radiation therapy? Results of phase III randomised trial.

PURPOSE: Radio-induced early skin reactions still remain a clinical challenge. Preliminary results with Hyaluronic acid, one of the most recent topical products used in this indication are proving interesting. To evaluate the efficacy of Hyaluronic acid compared to placebo. MATERIAL AND METHODS: Breast cancer patients with grade 1-2 radio-induced dermatitis during postoperative radiotherapy were eligible. They were randomised to receive either hyaluronic acid (A) or a simple emollient (B). The primary endpoint was the clinical evaluation of the erythema (success versus failure). Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. RESULTS: Two-hundred patients were enrolled (A=99, B=101). Ninety-five patients per treatment arm could be evaluated. Failures occurred in 23 patients (24%) in the hyaluronic acid arm, and 32 (34%) in the emollient arm (p=0.15). Seventy-three patients (36.5%) prematurely stopped the treatment without any ensuing difference between the two arms. Body mass index and the size of the epithelitis were both independently associated with the failure of the local treatment. The relative reduction of colorimetric levels was 20% in the hyaluronic acid group, and 13% in the emollient group (p=0.46). Concerning the quality of life assessment, there was a trend towards a lower level of pain in patients receiving hyaluronic acid (p=0.053). CONCLUSIONS: The present study showed no significant difference between hyaluronic acid and simple emollient in the treatment of acute radio-induced dermatitis. There was however a trend towards an improvement in both pain level and skin colorimetry.

Use of a subcutaneous implantable pleural port in the management of recurrent malignant pleurisy: five-year experience based on 168 subcutaneous implantable pleural ports.

INTRODUCTION: The authors report their experience in the use of subcutaneous implantable pleural port (SIPP) catheters for the treatment of symptomatic recurrent malignant pleurisy. MATERIALS AND METHODS: Single-center, prospective follow-up of 137 patients (168 SIPPs). RESULTS: No SIPP placement failures were observed. All but 3 of the 125 evaluable patients obtained complete or partial relief of their dyspnea. Seventy-six patients (60.3%) were receiving chemotherapy. Spontaneous pleurodesis was observed within 2 months in 46 patients (36.8%). Twenty-six patients (20.8%) died during the month following SIPP placement. Forty-one patients (32%) survived for more than 6 months. The overall median survival time was 344 days. Three infectious complications (1 empyema, 2 cellulitis) and 3 mechanical complications were observed. The role of pleurodesis as prognostic factor was assessed. Seventy-one patients survived for more than 2 months, 36 with pleurodesis, 35 without pleurodesis, requiring repeated pleural aspiration. The difference observed between the two groups by the 120th day was no longer significant when chemotherapy was taken into account. CONCLUSION: SIPP is a safe and effective option for the outpatient management of recurrent malignant effusions and could be considered as first-line treatment in all patients with bilateral, compressive pleural effusion or poor lung reexpansion.

Gastric metastasis of breast cancer: a single centre retrospective study.

BACKGROUND: Digestive metastasis of breast cancer are rare but when they do occur the stomach is one of the commoner sites. AIM: To describe the clinical, endoscopic, pathological features and treatment. METHODS: 35 cases of gastric metastasis were identified retrospectively between 1980 and 2008. RESULTS: The location of the gastric metastasis was fundus (n=15, 43%), antrum (n=15, 43%) or both (n=5, 14%). The histological subtype of primary breast cancer was invasive lobular carcinoma in 34 patients (97%). Hormonal receptors were positive in 19 out of 24 cases (79%), two out of 22 analysed were HER2 positive (9%). There were 16 (46%) patients with peritoneal carcinosis. The treatment was chemotherapy (n=13, 37%), hormonotherapy (n=2, 6%) or both (n=13, 37%). The 2-year survival rate after gastric metastasis diagnosis was 53% with a median follow up of 31 months [7-84 months]. CONCLUSION: Ninety-seven percent of gastric metastasis from breast cancers are derived from invasive lobular carcinoma. Seventy-nine percent of these are HER+ and comparison with the original histopathological slides of primary breast carcinoma should be performed to differentiate gastric metastasis from primary gastric carcinoma. Peritoneal carcinomatosis accompanied gastric metastasis in almost half the cases in this series and treatment was generally chemotherapy.

[Brain metastases in breast cancer. Epidemiology and natural history. The Institut Curie experience]. / Métastases cérébrales dans les cancers du sein. Épidémiologie et histoire naturelle. Expérience de l'Institut Curie à travers deux études : les patientes HER2- de moins de 65 ans et les patientes de plus de 65 ans.

Breast cancer is the second cause for brain metastases. Their incidence is rising, partly due to the therapeutic improvements which alter the natural history of breast cancer. Predictive factors for brain metastases have been identified: HER2 oncogene overexpression, lack of expression of hormone receptors, young age and triple negative status. Brain metastases prognosis remains poor with a median survival shorter than 1 year, except for solitary lesions treated by surgery or radiosurgery. We have analysed two series of data from Institut Curie (Paris and Saint-Cloud). In women younger than 65 years, with HER2 negative breast carcinoma, median survival was 7.1 months. In women older than 65 years, median survival was 4 months.

Concordant analysis of KRAS status in primary colon carcinoma and matched metastasis.

KRAS somatic mutations are the main predictive factor for non response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. We compared KRAS mutational status in the primary tumour and the corresponding metastases (1 to 4 sites) in 38 mCRC patients. KRAS mutational status was analysed using direct sequencing, SNAPShot multiplex PCR and Scorpion Taqman PCR analysis. Results showed 54% of primary tumours had KRAS mutations. A concordance of 97% between primaries and metastatic sites was observed. A tumour heterogeneity was also demonstrated in 5% of mCRC. One case with three different primary tumours harboured three different KRAS mutations, and only one was represented in the unique metastasis of this patient. We concluded there was a high concordance in the KRAS status between the primary tumour and metastases. More than one informative block and more sensitive assay may increase the accuracy of KRAS status determination.

Management of the post-breast-conserving therapy defect: extended follow-up and reclassification.

BACKGROUND: Suboptimal aesthetic outcomes after conservative therapy for breast cancer are not uncommon, with reported rates up to 30 percent, of which 5 percent may be considered severe. With radiotherapy being an essential component of breast-conserving therapy, surgical correction of deformities is challenging, and guidance as to reparative technique selection is currently limited. METHODS: One hundred forty-one patients have undergone surgical correction of breast-conserving therapy-induced deformity since its inception at our institution in 1991. This consecutive series has been analyzed with respect to surgical procedure, complications, revisional surgery, and aesthetic outcome (with a five-point scale) to July of 2008. RESULTS: The overall aesthetic result was considered to be at least satisfactory in 94.5 percent at 1 year and in 88.8 percent at 5 years. Secondary surgery was required in 19.1 percent and a third procedure was required in 6.4 percent. Complications were encountered in 14.2 percent. A classification into five grades of deformity was found to be practical and effective for surgical planning. CONCLUSIONS: Reparative surgery for aesthetic deformity in scarred and irradiated breasts is able to produce satisfactory aesthetic results; however, revisional surgery and complications are not inconsiderable, and the authors hope the new classification based on their long-term experience will provide practical guidance for surgical planning to other surgeons encountering such patients.

Oncoplastic breast surgery for cancer: analysis of 540 consecutive cases [outcomes article].

BACKGROUND: Synchronous plastic and oncological surgery is undertaken to improve the security of excision margins and yield high-quality aesthetic outcomes when conventional breast-conserving therapy either anticipates poor results or is not possible. METHODS: A total of 540 consecutive patients underwent primary oncoplastic breast surgery for cancer with high tumor-to-breast volume ratios and locations precluding a good aesthetic result with simple tumor excision. A variety of techniques were employed at the Institut Curie between 1986 and 2007, and aesthetic outcomes were assessed on a five-point scale from 1 (excellent) to 5 (poor). RESULTS: The median age was 52 years (range, 28 to 90 years), and median follow-up was 49 months (6 to 262 months). Median tumor size was 29.1 mm (range, 4 to 100 mm), with most patients (72.3 percent) having a brassiere cup size of B or C. Close or involved margins occurred in 18.9 percent, with mastectomy being necessary in 9.4 percent. A satisfactory aesthetic outcome (ratings of 1 to 3) at 5 years was obtained in 90.3 percent. Five-year overall and distant disease-free survival rates were 92.9 and 87.9 percent, respectively, with local recurrence in 6.8 percent. CONCLUSIONS: With local recurrence and survival rates similar to those for breast-conserving therapy, this series confirms the safety of oncoplastic breast surgery for tumors both high in volume and difficult in location. Highly satisfactory cosmetic outcomes extend the indications for conservative surgery, further reduce the mastectomy rate, and limit adverse aesthetic sequelae.

Does a geriatric oncology consultation modify the cancer treatment plan for elderly patients?

BACKGROUND: This study was performed to describe the treatment plan modifications after a geriatric oncology clinic. Assessment of health and functional status and cancer assessment was performed in older cancer patients referred to a cancer center. PATIENTS AND METHODS: Between June 2004 and May 2005, 105 patients 70 years old or older referred to a geriatric oncology consultation at the Institut Curie cancer center were included. Functional status, nutritional status, mood, mobility, comorbidity, medication, social support, and place of residence were assessed. Oncology data and treatment decisions were recorded before and after this consultation. Data were analyzed for a possible correlation between one domain of the assessment and modification of the treatment plan. RESULTS: Patient characteristics included a median age of 79 years and a predominance of women with breast cancer. About one half of patients had an independent functional status. Nearly 15% presented severe undernourishment. Depression was suspected in 53.1% of cases. One third of these patients had >2 chronic diseases, and 74% of patients took > or =3 medications. Of the 93 patients with an initial treatment decision, the treatment plan was modified for 38.7% of cases after this assessment. Only body mass index and the absence of depressive symptoms were associated with a modification of the treatment plan. CONCLUSION: The geriatric oncology consultation led to a modification of the cancer treatment plan in more than one third of cases. Further studies are needed to determine whether these modifications improve the outcome of these older patients.

[HRT in post menopausal women and breast cancer at the Institut Curie]. / Traitement hormonal substitutif de la ménopause et cancer du sein à l'Institut Curie entre 1988 et 1999.

Several recent papers have suggested the role of HRT in the development of breast cancers. From the data base of the Institut Curie we compared the clinical characteristics, histoprognosis factors and survival of a cohort of 6737 patients recorded between 1988 and 1999 in which 1482 declared having receive HRT for more than 6 months. Surgical procedure, locoregional recurrence, metastasis, disease free and global survival were compared bet the patient who received an HRT versus the patients who didn't receive this treatment Mammographic diagnosis was more frequent in the HRT group and the age at diagnosis was smaller (p < 10(-4)). Cancers diagnosed in the HRT group were smaller and had a more favourable biologic profile as well as there were more lobular carcinomas and the conservative treatment was more frequent (p < 10(-4)). Mean follow up was 97 months. Recurrence free survival was not different in the two groups but the metastasis free and global survival were better in the HRT group. HRT remained an independent prognostic factor in a multivariate analysis. In western countries the increasing incidence of breast cancer concerns pre as well as post menopausal women. HRT cannot be considered as the only responsible of this augmentation.