Cases Of Recurrent Breast Cancer Research Articles

P2-3-1 - Tle3 is a Useful Surrogate Marker for Predicting Eribulin Chemo-Sensitivity in Triple-Negative Breast Cancer

Background: Eribulin mesylate (eribulin) is a microtubule dynamics inhibitor having an action mechanism that differs from taxane and vinca alkaloid. Eribulin does not have cross resistance due to an action mechanism that differs from other taxane drugs. Moreover, because it was effective against TNBC upon sub-analysis at phase III clinical trial 301, it is expected to become the key drug for chemotherapy against TNBC in the future. In this study, we investigated predictive factors regarding the therapeutic effect in eribulin chemotherapy using factors such as TLE3, beta-tubulin class III, GSTP1, etc. previously reported as being predictive factors of the therapeutic effect of taxane drugs.Methods: The subjects were 52 inoperable or metastasis / recurrent breast cancer cases that underwent chemotherapy using eribulin. The clinical benefit rate (CBR) was calculated regarding the efficacy thereof. Morphologies such as tissue-type, nucleus grade, etc. were compared by hematoxylin and eosin staining and the expression of ER, PR, HER2, Ki67, beta-tubulin class III, GSTP1, and TLE3 was compared by immunostaining regarding a needle biopsy specimen infiltrate prior to treatment.Results: The clinical effects were CBR 46.2 per cent. According to the intrinsic subtype classification: Luminal A: 16 cases: Luminal B: 12 cases: Luminal HER2: 2 cases: HER2 enriched: 3 cases: and TNBC: 19 cases. When the clinicopathological background and expression of each factor were investigated, TNBC was observed with significantly higher expression of TLE3 compared to non-TNBC; however, no significant difference was observed regarding other factors. Further, breast cancer patients with TLE3 expression had significantly higher CBR. Meanwhile, no significant difference was observed in beta-tubulin class III and GSTP1 expression.Conclusions: Our findings therefore suggest that TLE3 may be useful as a marker for predicting the therapeutic effect in eribulin chemotherapy for TNBC.

A Case of Recurrent Breast Cancer with Solitary Metastasis to the Urinary Bladder

Elderly patients with breast cancer often present with symptomatic, locoregionally advanced rather than screening-detected disease, thereby increasing the risk of metastatic recurrence during their remaining life time. Typical sites of metastases include lungs, bones, liver, and brain. Here we present a patient who developed a solitary urinary bladder metastasis five years after primary diagnosis of stage T4 N0 estrogen receptor-positive lobular carcinoma, while on continued adjuvant endocrine treatment (91 years of age). Anemia and increased serum creatinine resulting from hydronephrosis led to diagnosis of metastatic disease, which was confirmed by transurethral resection. The patient responded clinically to palliative radiotherapy and a different type of endocrine therapy. One year after diagnosis of metastatic disease, she died without signs of cancer progression.

Recurrent breast cancer in the subpectoral space after implant reconstruction

Breast reconstruction after mastectomy is most commonly performed with a prosthetic implant placed beneath the pectoralis major. Recurrence may rarely be identified in the subpectoral space where the implant was placed. We report a case of recurrent breast cancer after implant-based reconstruction with isolated subpectoral recurrence discovered 5 years later during secondary revision of her reconstructed breast.

乳癌術後10年で多発骨転移と癌性髄膜炎で再発し急速な転帰を辿った1例

乳癌術後10年で多発骨転移と癌性髄膜炎で再発し急速な転帰を辿った1例

脳室-腹腔シャント経路の腹壁に再発した乳癌の1例

脳室-腹腔シャント経路の腹壁に再発した乳癌の1例

PD07-03: Phase II Trial of Adjuvant TC (Docetaxel/Cyclophosphamide) Plus Trastuzumab (HER TC) in HER2−Positive Early Stage Breast Cancer Patients.

Abstract Introduction: TC is an effective adjuvant chemotherapy regimen in early stage breast cancer (ESBC) patients. Jones et al (J Clin Oncol 2009 Mar 10;27(3): 1177–1183) demonstrated a significantly superior 5-year DFS and OS for TC compared to AC. Because TC was superior to AC in a subset analysis of HER2+ breast cancer treated without trastuzumab, we tested TC in combination with 1 year of trastuzumab in lower risk HER2+ ESBC, predominately node negative disease. Methods: This was an open-label, phase II study of TC+H in HER2+ patients based on HER2 overexpression determined at the local level. Tissue was collected for central review of HER2 and TOP2A status. There was no lower limit of tumor size for lymph node negative cancers. Every 21 days, patients received docetaxel (T) 75mg/m2 IV, plus cyclophosphamide (C) 600mg/m2 IV, plus weekly trastuzumab (H) 4mg/kg IV (loading dose) and 2mg/kg IV thereafter for a total of 4 cycles. After 4 cycles of TC+H, patients continued on H for a total of 1 year. Appropriate patients received radiotherapy. Cardiotoxicity (decreased left ventricular ejection faction) was assessed by MUGA or ECHO at baseline, at completion of TC+H, and then at 3-month intervals until completion of trastuzumab treatment. The primary endpoint was DFS at 2 years with continued follow-up for 3 years. Secondary endpoints were OS and safety. Results: 486 patients received treatment, and 397(82%) completed a full year of H. Median age was 55 years(range: 24–75.8), ECOG PS 0=426(87.7%) and 1=60(12.3%); 280(57.6%) were Stage 1, 200(41.2%) were Stage II, and 6(1.2%) were Stage III. Disease-free survival and OS at 2 and 3 years are listed in the table below according to various features. The most common Grade 3/4 toxicities were neutropenia (47.1%) and febrile neutropenia (6.2%). There were 5 deaths: 1 due to PD, 1 aspiration, and 1 respiratory distress syndrome (possibly related to treatment), 1 cardiopulmonary arrest, and 1 unknown. There were 13 cases of recurrent breast cancer (local 5, or local/distant 8). Cardiac dysfunction occurred in 28(5.8%) patients, with 12(2.5%) being Grade 1, 14(2.9%) Grade 2, and 2(0.4%) grades 3/4. Sixteen patients had to stop H due to cardiac dysfunction with H. Central assessment of TOP2A status was performed by FISH in 90% of cases: TOP2A-amplified (42%), deleted (27%), and normal (31%). However TOP2A status had no effect on outcome. Conclusions: 1) The HER TC regimen was evaluated in 486 patients with HER2 overexpressed ESBC and found to be effective at the primary endpoint of 2 years. 2) Efficacy was demonstrated in node negative cancer including 94 cancers <1 cm. 3) Toxicity was acceptable with a low rate of cardiac dysfunction, mainly reversible. 4) The HER TC regimen is an option for patients with lower risk HER2 overexpressing ESBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-03.

Functional Polymorphisms in UDP-Glucuronosyl Transferases and Recurrence in Tamoxifen-Treated Breast Cancer Survivors

Tamoxifen is oxidized by cytochrome-P450 enzymes (e.g., CYP2D6) to two active metabolites, which are eliminated via glucuronidation by UDP-glucuronosyl transferases (UGT). We measured the association between functional polymorphisms in key UGTs (UGT2B15*2, UGT2B7*2, and UGT1A8*3) and the recurrence rate among breast cancer survivors. We used the Danish Breast Cancer Cooperative Group registry to identify 541 cases of recurrent breast cancer among women with estrogen receptor-positive tumors treated with tamoxifen for at least 1 year (ER(+)/TAM(+)), and 300 cases of recurrent breast cancer among women with estrogen receptor-negative tumors who were not treated with tamoxifen (ER(-)/TAM(-)). We matched one control to each case on ER status, menopausal status, stage, calendar period, and county. UGT polymorphisms were genotyped from archived primary tumors. We estimated the recurrence OR for the UGT polymorphisms by using logistic regression models, with and without stratification on CYP2D6*4 genotype. No UGT polymorphism was associated with breast cancer recurrence in either the ER(+)/TAM(+) or ER(-)/TAM(-) groups [in the ER(+)/TAM(+) group, compared with two normal alleles: adjusted OR for two UGT2B15*2 variant alleles = 1.0 (95% CI, 0.70-1.5); adjusted OR for two UGT2B7*2 variant alleles = 0.96 (95% CI, 0.65-1.4); adjusted OR for one or two UGT1A8*3 variant alleles = 0.95 (0.49-1.9)]. Associations were similar within strata of CYP2D6*4 genotype. Functional polymorphisms in key tamoxifen-metabolizing enzymes were not associated with breast cancer recurrence risk. Our results do not support the genotyping of key metabolic enzyme polymorphisms to predict response to tamoxifen therapy.

Identification of recurrence-related microRNAs in the bone marrow of breast cancer patients

Recently, bone marrow has been considered as playing a critical role in the generation of both metastasis and recurrent disease. The accumulation of a single microRNA in the bone marrow has the potential to regulate the translation of multiple genes in cancer metastasis and may therefore serve as a prognostic marker for cancer recurrence. MicroRNA microarray analysis was performed to compare microRNA levels in bone marrow from 4 breast cancer patients with recurrent disease and 4 patients without recurrence. Accumulation of two of these microRNAs, miR-21 and miR-181a, in the recurrent breast cancer cases was validated by RT-PCR in bone marrow from 291 additional breast cancer cases. Expression of a common target gene, PDCD4, was also determined in bone marrow from 291 breast cancer cases. Increased miR-21 and miR-181a levels were significantly associated with shortened disease-free survival (DFS; p=0.0003, 0.0007) and overall survival (OS; p=0.0351, 0.0443), respectively. While low PDCD4 expression was also significantly associated with poorer DFS (p=0.036). Multivariate analysis identified bone marrow miR-21 and mR-181a levels as valuable independent prognostic factors, with correlation coefficients that were significantly higher than that of the transcript of their common target gene. Accumulation of miR-21 and miR-181a in bone marrow appears to be associated with prognosis in breast cancer patients. The much higher significant correlation with microRNA levels and prognosis suggests epistatic effects on multiple target genes in the bone marrow of breast cancer patients.

Should Internal Mammary Lymph Node Biopsy Be a Routine Step in Recurrent Breast Cancer? Report of Three Cases With Negative Axilla and Positive Internal Mammary Node

Lymph node status is the most important clinicopathological prognostic factor for breast cancer patients and in most breast units it reflects only the axillary lymph nodes. A second often overlooked basin consists of the internal mammary lymph nodes (IMLNs) whose evaluation is not done as a routine step during the staging process. We highlight the need to consider incorporation of IMLNs into a patient’s staging by presenting three cases of recurrent breast cancer with negative axilla and positive IMLN, a finding which altered their final management. We suggest that biopsy of IMLN should be a routine step in recurrent breast cancer when axillary lymphatics are disrupted by previous surgery although further research is required to define the optimal management of node positive cases.

A case of recurrent breast cancer suggesting chemotherapy affected the pain control with oxycodone

A case of recurrent breast cancer suggesting chemotherapy affected the pain control with oxycodone

Detection of locoregional and distant recurrences in breast cancer patients by using FDG PET.

Cases of recurrence of breast cancer can pose considerable diagnostic and therapeutic challenges for the oncologic team. The prognosis and management decisions are based on knowledge of the true extent of disease. Conventional staging methods, including physical examination, assessment of levels of tumor markers, cross-sectional imaging, and bone scintigraphy, may not reliably demonstrate the extent of disease in all cases. Physical examination and cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging) can be problematic because (a) the sequelae of previous surgery and radiation therapy can be difficult to distinguish from recurrent neoplasms and (b) early metastatic disease (small lesions) can be difficult to distinguish from benign lesions that are too small to characterize. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) can help clarify inconclusive findings from physical examination and cross-sectional imaging. FDG PET is more sensitive than CT in detection of lymphatic spread of disease to locoregional and mediastinal nodes. Metastases at distant sites including the lung, bone, and the liver are also readily detected at FDG PET. FDG PET has been proved accurate in restaging cases of recurrent breast cancer and will likely aid in directing therapy in these cases.

Determination of cytosol c-erbB-2 protein in breast cancer by sandwich enzyme immunoassay.

We determined cytosol c-erbB-2 protein levels using a sandwich enzyme immunoassay in benign breast disease and primary and recurrent breast cancer and analyzed the relationship between c-erbB-2 protein levels and clinicopathological factors. Overexpression of c-erbB-2 protein, the cut-off value being set at 18 ng/mg protein, was observed in 26 of the 139 cases of stages I-IIIB breast cancer (18.7%), four of the 12 cases of stage IV breast cancer (33.3%) and seven of the 13 recurrent breast cancer cases (53.8%). The levels of c-erbB-2 protein were significantly different between the stages. Overexpression of c-erbB-2 protein in stages I-IIIB breast cancer was associated with histological grade and serum CEA level, but not with other clinicopathological factors. In addition, there was an inverse correlation in the group of stages I-III plus IV breast cancer between c-erbB-2 protein expression and estrogen receptor status. Overexpression of c-erbB-2 protein can be easily determined in the cytosol fraction together with hormonal receptor by this method. The prognostic importance will be evaluated in ongoing adjuvant trials for operable breast cancer patients.

A RECURRENT BREAST CANCER CASE WITH BONE METASTASES DETECTED BY WHOLE BODY POSITRON EMISSION TOMOGRAPHY (PET)

We report a case of recurrent breast cancer with bone metastases, which were negative on skeletal bone survey or bone scintigram, and positive for whole body positron emission tomography (PET). A 48-year-old woman was admitted to our hospital because of left cervical lymphb node metastases. She had undergone modified radical mastectomy for left breast cancer 17 months previously. Chest X-ray, routine head CT scan, abdominal ultrasound, GI tract examinations, skeletal bone survery, and bone sctintigra-phy were performed, but there were no abnormal findings except left cervical lymph node swelling. Whole body PET was performed. It revealed abnormal accumulation not only in the left supraclavicular area but also in the cervical spine, Th-spine and L-spine. MRI revealed typical bone metastases of the spine. Whole body PET was useful for detecting bone metastases in this case.

A CASE OF RECURRENT BREAST CANCER TO THE ANTERIOR CHEST WALL 19 YEARS AFTER A STANDARD RADICAL MASTECTOMY

We report a case of recurrent breast cancer to the anterior chest wall 19 years after a radical mastectomy for a left breast cancer (T2n0M0, Stage I). A 67-year-old woman was seen at the hospital because of a gradually enlarging tumor in the anterior chest wall which strated 8 months before when she first noticed it. A needle biopsy cytology revealed class V and she was diagnosed as hoving recurrent breast cancer. After one cource of chemotherapy into the left internal thoracic artery and irradiation at 50Gy, a total layer resection of the chest wall involving the sternal body was carried out. The defect in the chest wall was reconstructed with Marlex mesh, acrylic resion and myocutaneous flap made of the pectoralis major muscle. Postoperative course was uneventful and there has been no sign of infection. It is thought that our procedure described here should be actively considered for the patient with local recurrence of breast cancer to the chest wall.

AN OPERATED CASE OF RECURRENT BREAST CANCER TO THE CHEST WALL 12 YEARS AFTER THE FIRST OPERATION

We experienced a case of recurrent breast cancer to the chest wall 12 years after the first operation. The patient was a 52-year-old woman. There was a previous history of undergoing a radical mastectomy for a right breast cancer (t2n1βM0, Stage II) in October, 1982. The histologic type was solid tubular carcinoma and the tumor was estrogen and progesterone receptor positive. In July, 1984, bilateral oophorectomy was carried out, followed by administration of tegafur and tamoxifen. The drug regimen was discontiuned in March, 1993, because she had no signs of recurrence. Two years later (in January, 1995), erosion associating with hemorrhage developed in the right anterior thoracic region. Close examination indicated a recurrence in the chest wall involving the right 4 and 5th ribs. After one course of CAF regimen excision of the chest wall with associated excision of the 3, 4 and 5th ribs ranging about 15 cm was carried out. A 15×8 cm defect in the chest wall was reconstructed with Marex mesh and latissimus dorsi muscle and skin flap. Postoperative course was uneventful. After two courses of CAF regimen, the patient was idscharged from the hospital. There has been no sign of recurrence, as of August, 1995, while tegafur and tagafur are still continued.

Prognostic factors in recurrent breast cancer: relationships to site of recurrence, disease-free interval, female sex steroid receptors, ploidy and histological malignancy grading

Site of first recurrence, disease-free interval (DFI), female sex steroid receptors, ploidy measurements as well as histological grading have been analysed as potentially valuable predictive factors in 313 cases of recurrent breast cancer. Univariate and multivariate analyses show histological grading, site of recurrence and disease free interval to be useful prognostic variables when assessing prognosis once disease has recurred. High concentrations of oestrogen receptors (ER) were found in patients with bone metastases, whereas lower concentrations of ER were related to visceral recurrences. Ploidy measurements failed in this study to give any predictive information once disease recurred.

Prognostic Analysis of Recurrent Breast Cancer

A total of 138 cases of recurrent breast cancer were reviewed to search for some prognostic factors especially in terms of types of recurrence. Solitary and "discrete" type chest wall recurrence presented the most favorable prognosis, giving an 88% survival rate at five years after recurrence, whereas multiple, disseminated and erysipelatoid type chest wall recurrence showed the poorest prognosis without any five-year survivors. It was also suggested that regional lymphatic recurrence was not as unfavorable as was expected, giving a 49% five-year survival rate. In cases of remote metastasis the five-year survival rate was 11% and no significant difference in prognosis was noticed among site-specific subgroups of remote recurrence. No significant effect of previous adjuvant radiotherapy on survival after recurrence was found and there was no correlation between the latent period and length of survival after recurrence.