Long-term results of fluorescence and indigo carmine blue dye-navigated sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy is widely applied for the management of clinically node-negative breast cancer, and a radioisotope with a blue dye are most often used as tracers. Fluorescence of indocyanine green could also potentially be used as tracer. This study aimed to demonstrate the long-term survival results of fluorescence-guided sentinel lymph node biopsy. PATIENTS AND METHODS: Patients with clinically node-negative breast cancer who underwent surgery as initial treatment were included in this study. Both fluorescence of indocyanine green and indigo carmine blue dye were used as tracers. Axillary lymph node dissection was omitted unless metastasis was pathologically proven in sentinel nodes. Breast cancer recurrence and death were recorded and prognostic factors were identified using disease-free survival and overall survival data. RESULTS: A total of 565 patients were analyzed. There were 14 (2.5%) patients whose sentinel nodes could not be identified, yielding an identification rate of 97.5%. Axillary dissection was performed in 90 patients. Forty-three recurrences including 6 ipsilateral axilla recurrence and 13 deaths were observed during the median 83 months of follow-up period. Seven-year disease-free and overall survival were 92.4% and 97.3%, respectively. Multivariate analyses demonstrated that pre-menopausal status and invasive lobular carcinoma were significant unfavorable prognostic factors of disease-free survival. Half of ipsilateral axilla recurrences occurred within 5 years after surgery and these recurrences were correlated with inappropriate adjuvant therapy. CONCLUSION: Fluorescence-guided sentinel lymph node biopsy demonstrated favorable prognostic results and could be alternative to the radioisotope for clinically node-negative breast cancer.

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B).

BACKGROUND: Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. METHODS: In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). RESULTS: The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1-28.0], DCR = 66.6% (95% CI 60.8-72.0), median PFS = 6.1 months (95% CI 5.3-6.7), median TTF = 5.1 months (95% CI 4.4-5.6), and median OS = 23.7 months (95% CI 20.7-27.4). CONCLUSION: The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

Risk Factors for Skin Flap Necrosis in Breast Cancer Patients Treated with Mastectomy Followed by Immediate Breast Reconstruction.

BACKGROUND: Skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) are the standard techniques for achieving a cosmetic outcome, but necrosis of a cutaneous flap including the nipple-areolar complex (NAC) is a serious complication. To analyze the risk factors for skin flap necrosis, we retrospectively evaluated a clinical database of breast cancer patients treated with mastectomy followed by immediate breast reconstruction. METHODS: Four hundred and twelve cases were consecutively recorded between 2006 and 2016. Body weight (BW), body mass index (BMI), distance from NAC to referent tumor, distance from overlying skin to the tumor and weight of breast resection (WBR) as measured in the operating theater were included in the statistical analysis. RESULTS: NSM, SSM and total mastectomy were performed in 123 (30%), 96 (23%) and 193 cases (47%), respectively. A tissue expander was used in 379 cases (92%), a silicone implant in 8 (2%) and autologous breast reconstruction in 25 (6%). Skin flap necrosis was found in 7% of all cases and NAC necrosis in 13% of NSM cases. In a univariate analysis, BW, NSM and WBR were risk factors for skin flap necrosis, and BW, BMI and WBR were risk factors for NAC necrosis. In a multivariate analysis, NSM and WBR remained significant risk factors for skin flap necrosis, and WBR was a significant risk factor for NAC necrosis. CONCLUSIONS: WBR is an important risk factor for skin flap necrosis. Especially, NAC necrosis should be considered for patients with large-volume breasts who undergo NSM and immediate breast reconstruction.

Progesterone receptor expression in proliferating cancer cells of hormone-receptor-positive breast cancer.

Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of estrogen-regulated genes, such as progesterone receptor, in proliferating cells. Progesterone receptor and Ki67 expressions were assessed by dual-fluorescence immunohistochemistry in estrogen-receptor-positive breast cancer tissues. Two distinct proliferating cell populations were observed: progesterone-receptor-positive and progesterone-receptor-negative. In the training cohort, tissues with progesterone-receptor-positive proliferating cells were associated with lower grade and better disease-free survival (p = 0.0055 and 0.0026, respectively). These associations were confirmed in the validation cohort from the neoadjuvant endocrine trial JFMC34 (p = 0.033 and 0.0003, respectively). In the validation cohort, patients with progesterone-receptor-positive proliferating cells responded better to endocrine therapy and had a lower Oncotype DX Recurrence Score. In the multivariate analysis, progesterone receptor status of proliferating cells, but not progesterone receptor or Ki67 alone, was an independent predictor of disease-free survival in both cohorts (p = 0.0043 and 0.0026). In conclusion, the progesterone receptor status of proliferating cancer cells was associated with histological grade and Recurrence Score, and a potent prognostic factor in estrogen-receptor-positive breast cancers. Results suggest that different driving systems generate different expression patterns of progesterone receptor in proliferating cancer cells. Further studies are warranted to validate the findings.

The Impact of Treatment Preferences in Second-Line Chemotherapy on the Prognosis of HER2-Negative Metastatic Breast Cancer.

OBJECTIVE: We assessed the impact of treatment preferences in second-line chemotherapy on breast cancer prognosis using the SELECT BC study. METHODS: The SELECT BC study was performed in patients with HER2-negative metastatic breast cancer treated with initial chemotherapy. From these patients, 618 were assigned to 2 groups (S-1 group, 309; taxane group, 309). The S-1 and taxane groups were each subdivided into 3 groups: crossover group, protocol-recommended group, and other group, and the analysis of overall survival (OS) was performed using Cox regression with inverse probability weighting, to adjust for postrandomization confounding. RESULTS: In the taxane group, the OS of the crossover group (39.6 months) was better than that of the protocol-recommended group (35.7 months) and the other chemotherapy group (36.9 months) (vs. the protocol-recommended group, HR 0.72 [95% CI 0.52-0.98], p = 0.037; vs. the other chemotherapy group, HR 0.71 [95% CI 0.43-1.18], p = 0.183). In the S-1 group, there was no statistically significant difference in OS between the 3 groups. CONCLUSION: The study of the combination of first-line chemotherapy and second-line chemotherapy showed that S-1 might be recommended as a second-line chemotherapy in patients in whom taxane was the primary chemotherapy.

Histopathologcial and clonal study of combined lobular and ductal carcinoma of the breast.

Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty-two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re-examination using immunostain of E-cadherin and ß-catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation-specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways.

Use of the neo-adjuvant exemestane in post-menopausal estrogen receptor-positive breast cancer: a randomized phase II trial (PTEX46) to investigate the optimal duration of preoperative endocrine therapy.

PURPOSE: The optimal treatment duration time and the causal relationship between neoadjuvant endocrine therapy and clinical response are not clear. Therefore, we conducted the present study to investigate the potential benefits of neoadjuvant exemestane therapy with the goal of identifying the optimal treatment duration. METHODS: This study was conducted at three hospitals, as a multicenter, randomized phase II trial(UMIN000005668) of pre-operative exemestane treatment in post-menopausal women with untreated primary breast cancer. Fifty-one post-menopausal women with ER-positive and/or PgR-positive invasive breast cancer were randomly assigned to exemestane for 4 months or 6 months. Clinical response, pathological response, and decisions regarding breast-conserving surgery were the main outcome measures. RESULTS: Of the 52 patients that enrolled, 51 patients underwent surgery. Of those, 26 and 25 patients had been treated with exemestane for 4 and 6 months, respectively. Treatments were performed at 3 hospitals in Japan between April 2008 and August 2010. The response rates as assessed by clinical examination were 42.3% and 48.0% for 4 and 6 months of treatment, respectively. Pathological responses (minimal response or better) were observed in 19.2% and 32.0% of patients, and breast-conserving surgery was performed on 50.0% and 48.0% of patients from the 4 and 6 month treatment groups, respectively. CONCLUSION: The results of this study demonstrate that responses were equal to 4 or 6 months of exemestane treatment. Therefore, we propose that the rates of breast-conserving surgery could be maximized by 4 months of treatment. Furthermore, in addition to using exemestane as a preoperative treatment in post-menopausal women with ER-positive breast cancer, we envision administering the drug over the long term under careful clinical supervision.

[Provision of information by pharmacists regarding the effective timing of co-administration of first-generation serotonin receptor antagonists and dexamethasone for chemotherapy-induced nausea and vomiting in patients receiving Doxorubicin and cyclophosphamide chemotherapy for breast cancer].

The combination of doxorubicin and cyclophosphamide is a standard chemotherapy regimen for breast cancer. Nausea and vomiting are two common adverse effects that may lead to a significant deterioration in the patient's quality of life. We report on the provision of information by pharmacists regarding the effective timing of the co-administration of first-generation serotonin receptor antagonists and dexamethasone for nausea and vomiting in patients receiving doxorubicin and cyclophosphamide (AC) chemotherapy for breast cancer. A total of 51 patients were enrolled in this study between January 2009 and December 2009. Vomiting was grade 0 in 34(67%)patients, grade 1 in 13(25%)patients, grade 2 in 3(6%)patients, and grade 3 in 1(2%)patient. Nausea was grade 0 in 17(33%)patients, grade 1 in 13(25%)patients, grade 2 in 13(25%) patients, and grade 3 in 15(29%)patients. The relative risk factors of vomiting were as follows: age, 1. 27; tumor size, 11. 05; node status, 1. 86; and chemotherapy, 0. 409. Only tumor size showed a significant difference(p=0. 006). The results of this study of 34 patients suggest that aprepitant may not be necessary for preventing AC chemotherapy. They showed that the provision of information by pharmacists regarding the effective timing of the co-administration of first-generation serotonin receptor-antagonists and dexamethasone is effective in patients who cannot take aprepitant.

Paradigm shift in axilla surgery for breast cancer patients treated with sentinel node biopsy.

BACKGROUND: Sentinel node biopsy (SNB) is a standard technique for the diagnosis of regional lymph node metastases in clinically node-negative breast cancer patients. In the case of pathologically negative sentinel lymph nodes (SLN), axillary lymph node dissection (ALND) can be avoided. METHODS: Recent clinical studies on SNB in breast cancer were reviewed regarding the pathological and molecular diagnosis of SLN, the tools used to predict non-SLN metastases, the prognostic significance of isolated tumor cells (ITC) and micrometastases (MIC), and axilla surgery. RESULTS: ITC or MIC in SLN was associated with worse survival in patients treated with SNB alone or SNB followed by ALND. However, this effect was limited and adjuvant therapy improved survival. If T1 and one SLN-positive breast cancer patients are treated with whole-breast irradiation and adjuvant therapy, additional ALND may not be necessary. CONCLUSIONS: SNB without ALND can be adopted for patients with a small number of SLN metastases. Although the lack of apparent regional lymph node recurrence, similar to tumor dormancy, cannot be fully explained, ALND should be performed in cases that are highly suspected to be non-SLN metastases.

[Predictive factors of nausea/vomiting of breast cancer patients receiving FEC and AC chemotherapy].

INTRODUCTION: It is largely believed that nausea/vomiting during cancer chemotherapy is caused by both the medical and personal factors of the patient. This study was aimed at examining whether the monitoring of risk factors prior to the therapy would help predict nausea/vomiting. METHOD: In the fifteen months between April 2006 and June 2007, breast cancer patients, receiving FEC and AC chemotherapy at the Outpatient Chemotherapy Room, were interviewed. Before they received their first treatment, each patient was asked to reply as to five risk factors: age, history of motion sickness, habitual drinking, history of morning sickness, and anxiety. Three weeks later, when they came back for their second treatment, CTCAE was conducted to assess their symptoms of nausea and vomiting. Fisher's exact probability test was used for the statistical analysis. RESULTS: 49 patients were studied. The relative risk ratios of vomiting were as follows: Age 1.57; motion sickness 2.15; habitual drinking 0.97; morning sickness 1.54; and anxiety 3.15. Only anxiety showed a significant difference(p=0.019). The associated risk ratios of nausea were: age 2.00; motion sickness 1.57; habitual drinking 1.04; morning sickness 1.37; and high levels of anxiety 2.28. Only anxiety showed a significant difference(p=0.018). The number of risk factors did not show a significant difference. CONCLUSION: The study shows that anxiety may be one of the risk factors that would cause severe nausea or vomiting during cancer chemotherapy.

Mammary ductoscopy by helical CT: initial experience.

BACKGROUND: An attempt was made to visualize minute intraductal lesions using helical CT in patients with abnormal nipple discharge. METHODS: Galactography was performed, immediately followed by CT (ductal CT examination). Based on the image data obtained, ductal images were constructed on a workstation using a Pegasus viewer (ductal CT imaging). Since no criteria for diagnosis by this method are available, ductal CT images were diagnosed by reference to the known ductal fiberscopic findings. RESULTS: Ductal CT examination was performed in 10 cases, in 9 of whom ductal CT images were successfully constructed. Pathological examination was performed in 8 cases. It was possible to observe the structure of the luminal surface on the constructed ductoscopic images from all directions, but the color tone or the presence or absence of hemorrhage could not be observed. CONCLUSIONS: In the examination for abnormal nipple discharge, ductal CT examination was useful for intraductal observation. Currently, it is a method that allows for observation of the most minute intraductal lesions. However, some issues still remain unresolved. The results of this study suggest that further studies with more cases hold the promise of making ductal CT imaging a useful examination method.