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1.
Strahlenther Onkol ; 195(4): 318-326, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30607453

ABSTRACT

PURPOSE: To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC). METHODS: Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50-50.4 Gy, with a boost up to 60-60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40-42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated. RESULTS: 20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy. CONCLUSION: Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up.


Subject(s)
Breast Neoplasms/radiotherapy , Carcinoma, Intraductal, Noninfiltrating/radiotherapy , Carcinoma, Lobular/radiotherapy , Hyperthermia, Induced , Neoplasm Recurrence, Local/radiotherapy , Radiotherapy, Adjuvant , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant , Cohort Studies , Combined Modality Therapy , Electrons/therapeutic use , Female , Humans , Mastectomy, Segmental , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Photons/therapeutic use , Prospective Studies
2.
J Surg Res ; 215: 55-59, 2017 07.
Article in English | MEDLINE | ID: mdl-28688661

ABSTRACT

BACKGROUND: Sentinel lymph node (SLN) biopsy is the current prognostic tool for clinically node-negative breast cancer patients. If the SLN reveals macrometastasis, axillary lymph node dissection (ALND) is recommended. However, the use of ALND in patients with micrometastasis is debated. The objective of this study was to assess the utilization of ALND in the treatment of micrometastatic breast cancer. METHODS: An IRB approved, retrospective study of a pooled dataset of breast cancer patients with micrometastatic disease on SLN biopsy was performed. Patients diagnosed from 1999-2016 were identified via query of a single-institution National Comprehensive Cancer Network (NCCN) breast cancer database as well as a prospective tumor board. RESULTS: A total of 91 patients were diagnosed with micrometastatic nodal disease. The median age at diagnosis was 56 y (range: 31-85); median follow-up time was 47 mo (range: 0-203 mo). 42/91(46.2%) patients had ALND of which 37/42 (88.1%) were a second operation; 3/42(7.1%) patients had additional positive nodes found at ALND. 44/91 (48.4%) patients received radiation. 7/91 (7.7%) patients had a recurrence, 5/7 local, including one axillary (2.1%; patient declined ALND). CONCLUSIONS: Given that the risk of lymphedema after ALND ranges between 20%-53%, the morbidity of ALND may far exceed the likelihood of detecting further nodal involvement in women with micrometastatic disease: 7.1% in this series.


Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/surgery , Lymph Node Excision/statistics & numerical data , Neoplasm Micrometastasis , Practice Patterns, Physicians'/statistics & numerical data , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Female , Florida , Follow-Up Studies , Humans , Lymphatic Metastasis , Middle Aged , Retrospective Studies , Treatment Outcome
3.
J Am Coll Surg ; 223(5): 717-728.e4, 2016 11.
Article in English | MEDLINE | ID: mdl-27788894

ABSTRACT

BACKGROUND: Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. STUDY DESIGN: Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. RESULTS: Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69-0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74-0.83). CONCLUSIONS: Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Guideline Adherence/statistics & numerical data , Mastectomy, Segmental , Practice Patterns, Physicians'/statistics & numerical data , Adult , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant/statistics & numerical data , Databases, Factual , Female , Humans , Middle Aged , Neoadjuvant Therapy/statistics & numerical data , Neoplasm Staging , Practice Guidelines as Topic , United States
4.
Eur J Surg Oncol ; 41(1): 94-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25245538

ABSTRACT

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on immediate free flap breast reconstruction remains controversial. Furthermore, the oncological outcomes of immediate free flap breast reconstruction after skin-sparing mastectomy (SSM) following NACT remain unclear. This study aimed to investigate the surgical complications and oncological outcomes of immediate perforator flap reconstruction after SSM following NACT. METHODS: A total of 201 consecutive patients with indications for immediate perforator flap reconstruction after SSM were included between 2004 and 2012. Surgical and oncological outcomes were compared between patients with and without NACT. RESULTS: There were 38 patients in the NACT group and 163 in the non-NACT control group. The median age of the NACT group was 39.5 years, which was significantly younger than the control group (43.0 years; P < 0.05). Patients in the NACT group also had more advanced and aggressive disease (P < 0.05). There was no significant difference in the frequency of surgical complications between the groups, no difference in the type of complications, and no significant difference in the frequencies of major and minor complications. No patients in the NACT group had delayed adjuvant therapy. Eight patients (4%) developed recurrences, with a median follow-up time of 3.0 years. Local recurrences occurred in three control patients but no patients in the NACT group. CONCLUSION: NACT does not affect short-term or interim outcomes after immediate perforator flap reconstruction and may thus represent a safe and practical treatment option for the multidisciplinary treatment of breast cancer.


Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Lobular/surgery , Mammaplasty/methods , Mastectomy, Subcutaneous/methods , Neoadjuvant Therapy , Perforator Flap , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carboplatin/therapeutic use , Carcinoma, Ductal, Breast/drug therapy , Chemotherapy, Adjuvant , Cohort Studies , Cyclophosphamide/therapeutic use , Docetaxel , Epirubicin/therapeutic use , Etoposide/therapeutic use , Female , Fluorouracil/therapeutic use , Humans , Middle Aged , Paclitaxel/administration & dosage , Retrospective Studies , Taxoids/administration & dosage , Trastuzumab , Treatment Outcome , Young Adult
5.
Ann Surg Oncol ; 22(1): 75-81, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25059792

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy (NCT) downstages advanced primary tumors, with magnetic resonance imaging (MRI) being the most sensitive imaging predictor of response. However, the impact of MRI evaluation on surgical treatment decisions in the neoadjuvant setting has not been well described. We report surgical patterns of care across 8 National Cancer Institute comprehensive cancer centers in women receiving both NCT and MRI to evaluate the impact of MRI findings on surgical planning. METHODS: Seven hundred seventy women from 8 institutions received NCT with MRI obtained both before and after systemic treatment. Univariate and multivariate analyses of imaging, patient-, and tumor-related covariates associated with choice of breast surgery were conducted. RESULTS: MRI and surgical data were available on 759 of 770 patients. A total of 345 of 759 (45 %) patients received breast-conserving surgery and 414 of 759 (55 %) received mastectomy. Mastectomy occurred more commonly in patients with incomplete MRI response versus complete (58 vs. 43 %) (p = 0.0003). On multivariate analysis, positive estrogen receptor status (p = 0.02), incomplete MRI response (p = 0.0003), higher baseline T classification (p < 0.0001), younger age (p < 0.0006), and institution (p = 0.003) were independent predictors of mastectomy. A statistically significant trend toward increasing use of mastectomy with increasing T stage at presentation (p < 0.0001) was observed in patients with incomplete response by MRI only. Among women with complete response on MRI, 43 % underwent mastectomy. CONCLUSIONS: Within a multi-institutional cohort of women undergoing neoadjuvant treatment for breast cancer, MRI findings were not clearly associated with extent of surgery. This study shows that receptor status, T stage at diagnosis, young age, and treating institution are more significant determinants of surgical treatment choice than MRI response data.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Magnetic Resonance Imaging , Mastectomy , Neoadjuvant Therapy , Adult , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/pathology , Carcinoma, Lobular/surgery , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Retrospective Studies , Young Adult
6.
Am Surg ; 80(7): 675-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24987899

ABSTRACT

Wire localized excision (WLE) has been a long-standing method for localization of nonpalpable breast lesions. Disadvantages of this method include difficulty locating the wire tip in relation to borders of the lesion, imprecise placement of the wire, and the need to place the wire shortly before scheduled surgery. These shortcomings may lead to a high positive margin rate requiring re-excision to obtain clear margins for breast cancer. Radioactive seed localized excision (RSLE) of nonpalpable breast lesions has been advocated as a safe and effective alternative to WLE. The primary endpoints of the study were to compare re-excision rates between WLE and RSLE of nonpalpable breast lesions and to determine if there were any differences in volume of tissue removed. One hundred three patients were included in a retrospective review of localized breast excisions done by a single surgeon. Forty-four patients underwent WLE between April 2007 and February 2009. Fifty-nine patients underwent RSLE between September 2009 and January 2012. Margins were considered to be clear if at least 1 mm of normal tissue was obtained from the circumferential periphery of the lesion in question. RSLE resulted in a re-excision rate of 17 versus 55 per cent re-excision rate for wire localization (P < 0.001). Excision volume was greater for patients having wire localization (P = 0.074). RSLE is an effective technique for excision of nonpalpable breast lesions in the community setting. This technique allows for accurate localization and appears to allow for smaller volume of tissue to be excised.


Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Lobular/surgery , Iodine Radioisotopes , Mastectomy, Segmental/methods , Radiopharmaceuticals , Adult , Aged , Breast Neoplasms/diagnostic imaging , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging , Carcinoma, Lobular/diagnostic imaging , Female , Humans , Middle Aged , Radionuclide Imaging , Reoperation , Retrospective Studies , Treatment Outcome
7.
Ann Surg Oncol ; 21(10): 3317-23, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25059788

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. METHODS: Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. RESULTS: There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). CONCLUSIONS: TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.


Subject(s)
Adenocarcinoma, Mucinous/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/mortality , Carcinoma, Lobular/mortality , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/surgery , Adult , Aged , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/surgery , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Prospective Studies , Survival Rate
8.
Breast ; 22(6): 1189-93, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24054903

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the benefit of Oncoplastic Breast Conserving Surgery (BCS) compared to standard BCS after primary CT, in terms of oncologic safety and cosmetic outcomes. BACKGROUND: The development of new drugs has led to greater use of primary chemotherapy (CT) for bulky breast cancer (BC) and has allowed wider indications for conservative surgery. PATIENTS AND METHODS: We identified 259 patients consecutively treated with BCS for primary BC from January 2002 to November 2010. All patients had undergone Oncoplastic Breast Surgery (OBS) or standard BCS after primary CT. Mastectomy rates, and oncological and cosmetic outcomes were compared. RESULTS: A total of 45 OBS and 214 standard BCS were analyzed. The median tumor size was 40 mm in the two groups (p = 0.66). The median operative specimen volumes were larger in the OBS group than in the standard group (respectively, 180 cm3 and 98 cm3, p < 0.0001). Re-excision (9% vs. 2%) and mastectomy (24% vs. 18%) rates were similar (p = 0.22 and p = 0.30) in the standard BCS group and in the OBS group respectively. At a median follow-up of 46 months, local relapse (p = 0.23) and distant relapse (p = 0.35) rates were similar. CONCLUSION: OBS allows excision of larger volumes of residual tumor after primary CT. OBS outcomes results were similar to those of standard BCS. Oncoplastic Breast Conserving Surgery (BCS) after primary chemotherapy allows wider breast resection than standard BCS. Survival and relapse probabilities are similar in both groups.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/surgery , Mastectomy, Segmental/methods , Anthracyclines/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/pathology , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Disease-Free Survival , Docetaxel , Esthetics , Female , Fluorouracil/administration & dosage , Humans , Mastectomy, Segmental/adverse effects , Neoadjuvant Therapy , Reoperation , Retrospective Studies , Taxoids/administration & dosage , Tumor Burden
9.
Ann Surg Oncol ; 20(8): 2569-75, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23463088

ABSTRACT

BACKGROUND: Radioguided occult lesion localization (ROLL) with technetium-99 m colloid (ROLL-(99m)Tc) is commonly used to perform breast-conserving surgery in patients with nonpalpable breast tumors. Radioactive seed localization is a relatively new technique that localizes the tumor with a radioactive iodine-125 ((125)I) seed. The feasibility and outcome of these techniques after neoadjuvant systemic treatment has not been widely investigated. METHODS: All patients treated with neoadjuvant systemic treatment between 2007 and 2010 in the Netherlands Cancer Institute who underwent breast-conserving surgery with the ROLL-(99m)Tc technique (n = 83) or with (125)I seed localization (n = 71) were analyzed. The weight of the resected specimen, the margins, and the percentage of patients requiring a second surgical intervention as a result of positive margins were assessed. RESULTS: Patient and tumor characteristics and systemic treatment regimens were comparable between both groups. The median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7 vs. 8 %) did not differ significantly between patients treated with the ROLL-(99m)Tc technique and (125)I seed localization. CONCLUSIONS: The ROLL-(99m)Tc technique and (125)I seed localization demonstrate comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Because (125)I seed localization does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling. Therefore, we prefer (125)I seed localization to perform breast-conserving surgery after neoadjuvant systemic treatment.


Subject(s)
Breast Neoplasms/diagnostic imaging , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Lobular/diagnostic imaging , Iodine Radioisotopes , Radiopharmaceuticals , Technetium Tc 99m Aggregated Albumin , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant , Female , Humans , Magnetic Resonance Imaging , Mastectomy, Segmental , Middle Aged , Neoadjuvant Therapy , Neoplasm, Residual , Radiology, Interventional/methods , Radionuclide Imaging , Reoperation
11.
Am J Clin Oncol ; 35(3): 242-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21358298

ABSTRACT

OBJECTIVES: Breast cancer treatment relies on 3 major phenotypical subtypes, including the triple-negative (TN), HER2-positive, and hormone receptor-positive (estrogen receptor/progesterone receptor) ones. We retrospectively determined the clinical and pathologic response rates to intensified taxane-free neoadjuvant chemotherapy according to these phenotypical classes in a series of patients with highly proliferative operable breast cancer, and examined the patterns of recurrence. METHODS: Patients with early breast cancer with highly proliferative (S-phase fraction >4%) operable tumors of >3 cm received 4 cycles of intensified neoadjuvant chemotherapy with high-dose cyclophosphamide (doxorubicin 70 mg/m d1, cyclophosphamide 700 mg/m d1/d8, and 5 FU 700 mg/m d1-d5) every 3 weeks. RESULTS: Fifty-five patients were included in the analysis. Patients with TN phenotype experienced a high pathologic complete response (pCR) rate to intensified chemotherapy in comparison with patients with HER2-positive and estrogen receptor/progesterone receptor tumors (47%, 0%, and 12%, respectively). Forty percent of patients with TN breast cancer recurred after a median follow-up of nearly 11 years, but only 22% of those achieving a pCR. CONCLUSIONS: A high pCR rate to short intensified neoadjuvant chemotherapy with high-dose cyclophosphamide was achieved in patients with operable highly proliferative TN breast cancer, and pCR was associated with a low rate of recurrence.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Neoadjuvant Therapy , Neoplasm Recurrence, Local/pathology , S Phase/physiology , Adult , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/surgery , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies
12.
Oncology ; 80(3-4): 269-77, 2011.
Article in English | MEDLINE | ID: mdl-21734419

ABSTRACT

OBJECTIVES: Individualized chemotherapy for breast cancer improves the outcome. Anthracyclines target the enzyme topoisomerase IIα (TOP2A). We set out to perform a retrospective study of the presence of gene abnormalities and the expression of TOP2A in a cohort of breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. METHODS: Forty-three patients with 45 breast cancers were treated with neoadjuvant docetaxel-epirubicin with/without capecitabine chemotherapy. The TOP2A status of the cancers, determined retrospectively by fluorescent in situ hybridization and immunohistochemistry, was analyzed in relation to the standard clinical and pathological data. RESULTS: Clinically and pathologically complete remission (pCR) was achieved in 15 (33.3%) and 9 (20%) cases, respectively. The TOP2A gene was amplified in 2 human epidermal growth factor receptor 2 (HER2)-positive cancers (8%), and 32 (84.2%) overall exhibited TOP2A expression in >15% of the cells. The expression of TOP2A exhibited a strong correlation with the expression of Ki67 (R = 0.743, p < 0.001), and was negatively correlated with estrogen receptors (ER; R = 0.404, p = 0.012) and progesterone receptors (R = 0.430, p = 0.007). The expression of TOP2A was not related to the amplification of the TOP2A gene or the HER2 status of the tumor. The proportions of Ki67- and TOP2A-positive tumor cells were significantly reduced after chemotherapy (56.1 ± 23.6 vs. 19.0 ± 27.7%, p = 0.004, and 41.0 ± 27.9 vs. 12.7 ± 24.8%, p < 0.001, respectively). The development of pCR was related to a high grade (p = 0.054), ER negativity (p = 0.027) and high TOP2A expression (p = 0.037). The expression of TOP2A was an independent predictor of pCR (OR = 1.460, for every 10% increase, 95% CI: 1.016-2.096, p = 0.041). After a median follow-up time of 31.0 months, neither relapse-free survival nor overall survival was related to the tumor response. CONCLUSIONS: TOP2A expression is a marker of the tumor's proliferation rate and sensitivity to anthracycline-based chemotherapy, and does not depend on the amplification of its gene.


Subject(s)
Antigens, Neoplasm/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/metabolism , DNA Topoisomerases, Type II/metabolism , DNA-Binding Proteins/metabolism , Adult , Antigens, Neoplasm/genetics , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/surgery , Capecitabine , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/genetics , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant , DNA Topoisomerases, Type II/genetics , DNA-Binding Proteins/genetics , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Docetaxel , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Gene Expression , Genes, erbB-2/genetics , Humans , Immunochemistry , In Situ Hybridization, Fluorescence , Ki-67 Antigen/metabolism , Middle Aged , Neoadjuvant Therapy , Poly-ADP-Ribose Binding Proteins , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Survival Analysis , Taxoids/administration & dosage , Treatment Outcome
13.
Ann Surg Oncol ; 17(10): 2690-5, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20422461

ABSTRACT

BACKGROUND: In breast cancer surgery, intraoperative frozen section (FS) analysis of sentinel lymph nodes (SLNs) enables axillary lymph node dissection (ALND) during the same operative procedure. In case of discordance between a "negative" FS analysis and definitive histology, an ALND as a second operation is advocated since additional lymph node metastases may be present. The clinical implications of the subsequent ALND in these patients were evaluated. MATERIALS AND METHODS: Between November 2000 and May 2008, 879 consecutive breast cancer patients underwent surgery including sentinel lymph node biopsy (SLNB) with intraoperative FS analysis of 2 central cuts from axillary SLNs. Following fixation and serial sectioning, SLNs were further examined postoperatively with hematoxylin and eosin (H&E) and immunohistochemical techniques. For patients with a discordant FS examination, the effect of the pathology findings of the subsequent ALND specimen on subsequent nonsurgical therapy were evaluated. RESULTS: FS analysis detected axillary metastases in the SLN(s) in 200 patients (23%), while the definitive pathology examination detected metastases in SLNs in another 151 patients (17%). A complementary ALND was performed in 108 of the 151 patients with discordant FS. Additional tumor positive axillary lymph nodes were found in 17 patients (16%), leading to "upstaging" in 7 (6%). Subsequent nonsurgical treatment was adjusted in 4 patients (4%): all 4 had more extensive locoregional radiotherapy; no patient received additional hormonal and/or chemotherapy. CONCLUSION: Discordance between intraoperative FS analysis and definitive histology of SLNs is common. In this selection of patients, a substantial proportion had additional lymph node metastases, but postsurgical treatment was rarely adjusted based on the findings of the complementary ALND.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/surgery , Frozen Sections/standards , Lymph Node Excision , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Axilla , Carcinoma, Ductal, Breast/secondary , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/secondary , Carcinoma, Lobular/surgery , Female , Follow-Up Studies , Humans , Intraoperative Period , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Prognosis , Prospective Studies
14.
Ned Tijdschr Geneeskd ; 153: A56, 2009.
Article in Dutch | MEDLINE | ID: mdl-19900317

ABSTRACT

OBJECTIVE: To establish the frequency of re-excision or mastectomy in women who had breast-conserving treatment for invasive lobular mammary carcinoma. DESIGN: Retrospective. METHOD: Data on the number of patients with invasive carcinoma from 1998-2006 were obtained from the national pathology database (PALGA) and the Dutch Comprehensive Cancer Centre East. The following data on patients who had undergone breast-conserving treatment for invasive lobular carcinoma were collected from the electronic patient records: age, localization procedure with wire-localisation and tumour size. RESULTS: The frequency of re-excision or mastectomy following initial breast-conserving surgery in 123 patients with invasive lobular carcinoma was 46.3 % versus 31.5 % in 877 patients with other types of invasive carcinoma. The number of re-excisions was higher in the group with invasive non-lobular carcinoma (4.9% versus 9.2%), and the number of conversions to mastectomy was higher in the group with invasive lobular carcinoma (41.5% versus 20.1%). The age of the patient, the localisation procedure and tumour size were not significant predictors of a tumour-free surgical margin or for the necessity of re-excision. CONCLUSION: The frequency of re-excision in patients with invasive lobular carcinoma was higher than in patients with other types of breast cancer. There was no statistically significant predictor for obtaining a tumour-free surgical margin.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/surgery , Mastectomy, Segmental , Breast/pathology , Female , Humans , Mastectomy , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging , Reoperation , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
15.
Ann Surg Oncol ; 14(10): 2946-52, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17514407

ABSTRACT

BACKGROUND: The optimal strategy for incorporating lymphatic mapping and sentinel lymph node biopsy into the management of breast cancer patients receiving neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node biopsy performed following neoadjuvant chemotherapy have largely reported on patients whose prechemotherapy, pathologic axillary nodal status was unknown. We report findings using a novel comprehensive approach to axillary management of node-positive-patients receiving neoadjuvant chemotherapy. METHODS: We evaluated 54 consecutive breast cancer patients with biopsy-proven axillary nodal metastases at the time of diagnosis that underwent lymphatic mapping with nodal biopsy as well as concomitant axillary lymph node dissection after receiving neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer center between 2001 and 2005. RESULTS: The sentinel node identification rate after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had residual axillary metastases (including eight patients that had undergone resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases (31%) the residual metastatic disease was limited to the sentinel lymph node. The final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three cases (8.6%). The negative final sentinel node accurately identified patients with no residual axillary disease in 17 cases (32%). CONCLUSIONS: Sentinel lymph node biopsy performed after the delivery of neoadjuvant chemotherapy in patients with documented nodal disease at presentation accurately identified cases that may have been downstaged to node-negative status and can spare this subset of patients (32%) from experiencing the morbidity of an axillary dissection.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Lymphatic Metastasis/pathology , Neoadjuvant Therapy , Neoplasms, Multiple Primary/drug therapy , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/radiotherapy , Carcinoma, Lobular/surgery , Combined Modality Therapy , Female , Humans , Lymph Node Excision , Lymph Nodes/pathology , Middle Aged , Neoplasm Staging , Neoplasm, Residual/pathology , Neoplasm, Residual/radiotherapy , Neoplasm, Residual/surgery , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/radiotherapy , Neoplasms, Multiple Primary/surgery , Predictive Value of Tests , Radiotherapy, Adjuvant , Treatment Outcome
16.
Zhonghua Zhong Liu Za Zhi ; 29(11): 871-4, 2007 Nov.
Article in Chinese | MEDLINE | ID: mdl-18396651

ABSTRACT

OBJECTIVE: To evaluate tolerance and toxicity of high-dose epirubicin regimen CEF-100 as adjuvant therapy for breast cancer. METHODS: From March 2005 to October 2006, 98 patients with stage I - III a breast cancer were randomly assigned to receive postoperative chemotherapy with CEF-100 regimen (epirubicin 100 mg/m2, dl per 21 days for 6 cycles, n =48) or CEF-60 regimen (epirubicin 60 mg/m2, dl per 21 days for 6 cycles, n = 50). Blood routine test were done every cycle, liver and kindey function were examined and adverse effects were recorded after every cycle. RESULTS: No difference of average leucocyte or neutrophil count (P >0.05) was observed in every cycle. Adverse effects of digestive tract and damage of liver function in CEF-100 group were more severe than that in CEF-60 group (P <0.05), but all adverse effects could be relieved by treatment. No severe non-hematological toxicity and cardiac toxicity in both groups were observed (P <0.05). There was no death caused by chemotherapy. CONCLUSION: Our data shows that high dose epirubicin-containing CEF regimen is safe and tolerable for postoperative chemotherapy of breast cancer patient, and the adverse effects could be relieved by marrow support and liver-protection therapy. Further observation and longer follow-up is still needed in order to evaluate the efficacy of this high dose regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Epirubicin/administration & dosage , Adult , Alanine Transaminase/blood , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aspartate Aminotransferases/blood , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Epirubicin/adverse effects , Epirubicin/therapeutic use , Female , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Follow-Up Studies , Humans , Leukopenia/chemically induced , Middle Aged , Neutropenia/chemically induced , Vomiting/chemically induced
17.
Magy Onkol ; 50(1): 19-23, 2006.
Article in Hungarian | MEDLINE | ID: mdl-16617379

ABSTRACT

INTRODUCTION AND AIMS: The feasibility, accuracy and clinical significance of sentinel lymph node biopsy for patients with breast cancer after neoadjuvant chemotherapy has not yet been determined. The aim of this study was to investigate these questions. PATIENTS AND METHOD: Dual agent-guided sentinel lymph node biopsy with preoperative lymphoscintigraphy was performed on 17 breast cancer patients after neoadjuvant chemotherapy at the Department of General and Thoracic Surgery, National Institute of Oncology, Budapest, from April 2004 to August 2005. Patients with clinically lymph node-negative breast cancer less than 3 cm in size after neoadjuvant chemotherapy were enrolled in the study. RESULTS: Lymphoscintigraphy showed no axillary lymphatic drainage in 7 patients (41%), and no sentinel lymph node could be identified during surgery in these patients. Axillary lymph nodes were histologically positive in 6 (86%) out of these 7 patients. Sentinel lymph node biopsy was successful in 10 patients (59%), and in 8 (80%) of them the sentinel lymph node proved to be positive pathologically. False negative sentinel lymph node biopsy did not occur. Axillary lymph node status was histologically positive in 14 (82%) out of the 17 patients. The predictable value of the clinical examination of the axilla after neoadjuvant chemotherapy, for the histological nodal status, was very low. DISCUSSION AND CONCLUSIONS: Our sentinel lymph node identification rate is lower than the published average in the literature. This difference can be explained by the differences in the indication for neoadjuvant chemotherapy. Our false negative rate (0%) is, however, significantly better than that of others. On the basis of international experiences sentinel lymph node biopsy after neoadjuvant chemotherapy is technically feasible, but its accuracy is not satisfactory and its clinical significance has not yet been determined. Our success rate is specifically low, which cannot be explained by the lack of practice. Taking the histologically very high axillary positive rate into consideration, sentinel lymph node biopsy has no clinical role in our practice after neoadjuvant chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Lymph Nodes/pathology , Neoadjuvant Therapy/methods , Sentinel Lymph Node Biopsy , Adult , Aged , Axilla , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant , Feasibility Studies , Female , Humans , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Predictive Value of Tests
18.
Ann Oncol ; 17(1): 65-73, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16361531

ABSTRACT

BACKGROUND: The purpose was to compare disease-free survival (DFS) between epirubicin-based chemoendocrine therapy and tamoxifen alone in one to three node-positive (N1-3), estrogen-receptor-positive (ER+), postmenopausal early breast cancer (EBC) patients. PATIENTS AND METHODS: We analyzed, retrospectively, 457 patients randomized in FASG 02 and 07 trials who received: tamoxifen alone (30 mg/day, 3 years); or FEC50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2, cyclophosphamide 500 mg/m2, six cycles every 21 days) plus tamoxifen started concurrently. Radiotherapy was delivered after the third cycle in FASG 02 trial, and after the sixth in FASG 07 trial. RESULTS: The 9-year DFS rates were 72% with tamoxifen and 84% with FEC50-tamoxifen (P = 0.008). The multivariate analysis showed that pathological tumor size >2 cm was an independent prognostic factor (P = 0.002), and treatment effects remained significantly in favor of chemoendocrine therapy (P = 0.0008). The 9-year overall survival rates were 78% and 86%, respectively (P = 0.11). In the multivariate model, there was a trend in favor of chemoendocrine therapy (P = 0.07). CONCLUSION: The addition of FEC50 adjuvant chemotherapy to tamoxifen significantly improves long-term DFS in N1-3, ER+ and postmenopausal women. Chemoendocrine therapy seems to be more effective than tamoxifen in terms of long-term survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Lymph Nodes/pathology , Receptors, Estrogen/metabolism , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/radiotherapy , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Disease-Free Survival , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Middle Aged , Neoplasms, Second Primary/etiology , Postmenopause , Retrospective Studies , Survival Rate , Tamoxifen/administration & dosage
19.
Hematology ; 11(3): 153-5, 2006 Jun.
Article in English | MEDLINE | ID: mdl-17326321

ABSTRACT

We report a breast cancer patient who developed acute myeloid leukemia (AML) one year following her adjuvant chemotherapy consisting of cyclophosphamide, adriamycin and 5-fluorouracil. Cytogenetic examination of bone marrow samples resulted in t(8;16)(p11.2;p13.3), which is a chromosome rearrangement observed in de novo and treatment related AML M4/M5 with a poor prognosis.


Subject(s)
Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Chromosomes, Human, Pair 16/ultrastructure , Chromosomes, Human, Pair 8/ultrastructure , Estrogens , Leukemia, Myelomonocytic, Acute/pathology , Neoplasms, Hormone-Dependent/drug therapy , Neoplasms, Multiple Primary/drug therapy , Neoplasms, Second Primary/pathology , Translocation, Genetic , Anastrozole , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/pathology , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/radiotherapy , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant/adverse effects , Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 8/genetics , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cytarabine/administration & dosage , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Fatal Outcome , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Idarubicin/administration & dosage , Leukemia, Myelomonocytic, Acute/chemically induced , Leukemia, Myelomonocytic, Acute/drug therapy , Leukemia, Myelomonocytic, Acute/genetics , Mastectomy, Modified Radical , Middle Aged , Neoplasms, Hormone-Dependent/pathology , Neoplasms, Hormone-Dependent/surgery , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/radiotherapy , Neoplasms, Multiple Primary/surgery , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/genetics , Nitriles/therapeutic use , Radiotherapy, Adjuvant , Triazoles/therapeutic use
20.
Chir Ital ; 57(5): 625-9, 2005.
Article in Italian | MEDLINE | ID: mdl-16241094

ABSTRACT

Preoperative localisation of non-palpable breast lesions is necessary for excisional biopsies. This can be achieved with methods such as anchor wire, charcoal marking, or radio-guided localisation. The aim of the present study was to evaluate retrospectively our experience with the wire localisation technique. One hundred and eighty-two patients with non-palpable breast lesions (diameter: 0.4-1.5 cm) were operated on under local anaesthesia. Intraoperative X-rays were performed in all cases. No serious perioperative complications occurred. Three patients (2 with postoperative haematomas and 1 with wound infection) underwent conservative therapy. The lesions were benign in 67/182 patients (37%), ductal and/or lobular invasive cancer in 42 (23%), carcinoma in situ in 23 patients (12.5%) and ADH-ALH in 50 patients (27.5%). Our experience confirms that wire localisation biopsies constitute an excellent method for the excision of non-palpable breast lesions. This technique is characterised by high reliability (100% total excisions) and assures a prognostic evaluation of high-risk lesions such as ductal an/or lobular atypical hyperplasia.


Subject(s)
Biopsy/methods , Breast Diseases/pathology , Breast Neoplasms/pathology , Breast/pathology , Carcinoma in Situ/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Adult , Aged , Anesthesia, Local , Breast Diseases/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Carcinoma in Situ/diagnostic imaging , Carcinoma in Situ/surgery , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/diagnostic imaging , Carcinoma, Lobular/surgery , Diagnosis, Differential , Female , Humans , Hyperplasia/pathology , Mammography , Middle Aged , Postoperative Complications , Prognosis , Retrospective Studies , Risk Factors
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