Akiyo Yoshimura

Occult breast cancer may originate from ectopic breast tissue present in axillary lymph nodes

PurposeOccult breast cancer (OBC) is classified as a carcinoma of unknown primary, and involves axillary lymphadenopathy and is histologically consistent with metastatic breast cancer. OBC has been conventionally considered as a metastatic lymph node lesion, the origin of which is an undetectable breast tumor. Therefore, OBC patients would usually have undergone axillary lymph node dissection, and mastectomy or whole breast radiotherapy (WBRT). However, majority of OBC reports have been based on cases that were diagnosed during a period when diagnostics was still relatively primitive, and when magnetic resonance imaging was not yet a standard preoperative assessment. Therefore, there have been many false negatives in the breast based on preoperative assessment.MethodsWe herein hypothesize that the origin of OBC is ectopic breast tissue present in axillary lymph nodes (ALNs). If our hypothesis is true, mastectomy and WBRT may be unnecessary for OBC patients.ResultsOur hypothesis is supported by several findings. First, advances in radiological imaging have suggested that a primary breast tumor is absent in OBC patients. Second, proliferative breast lesions arising from ectopic breast present in ALNs have been reported. Lastly, cellular subtypes in OBC based on immunohistochemistry are of various types including ordinary breast cancer and the prognosis is not worse than stage II breast cancer.ConclusionIt is important to distinguish between “primary” OBC in ALNs and “metastatic” OBC from micro-primary breast tumor. Further studies are required to determine if omission of mastectomy and WBRT is acceptable.

Recent Improvement in the Long-term Survival of Breast Cancer Patients by Age and Stage in Japan

Background Recent improvements in 5-year survival of breast cancer have been reported in Japan and other countries. Though the number of long-term breast cancer survivors has been increasing, recent improvements in 10-year survival have not been reported. Moreover, the degree of improvement according to age and disease stage remains unclear. Methods We calculated long-term survival using data on breast cancer diagnosed from 1993 through 2006 from six prefectural population-based cancer registries in Japan. The recent increase in 10-year relative survival was assessed by comparing the results of period analysis in 2002–2006 with the results of cohort analysis in 1993–1997. We also conducted stratified analyses by age group (15–34, 35–49, 50–69, and 70–99 years) and disease stage (localized, regional, and distant). Results A total of 63,348 patients were analysed. Ten-year relative survival improved by 2.4% (76.9% vs 79.3%) from 1993 through 2006. By age and stage, 10-year relative survival clearly improved in the age 35–49 years (+2.9%; 78.1% vs 81.0%), 50–69 years (+2.8%; 75.2% vs 78.0%) and regional disease (+3.4%; 64.9% vs 68.3%). In contrast, the degree of improvement was small in the age 15–34 years (+0.1%; 68.2% vs 68.3%), 70–99 years (+1.0%; 87.6% vs 88.6%), localized disease (+1.1%; 92.6% vs 93.7%) and distant metastasis (+0.9%; 13.8% vs 14.7%). Conclusions These population-based cancer registry data show that 10-year relative survival improved 2.4% over this period in Japan. By age and stage, improvement in the age 15–34 years and distant metastasis was very small, which suggests the need for new therapeutic strategies in these patients.

The investigation study using a questionnaire about the employment of Japanese breast cancer patients

Background Breast cancer is the most common cancer among women, and its survival rate has improved. As the number of cancer survivors increases, it is important to support their social comeback during and after treatment. Methods Questionnaires were distributed to breast cancer patients treated in Aichi Cancer Center Hospital between June and November 2014. Responders were categorized according to adjuvant therapy (Group A: none, Group B: endocrine therapy, Group C: chemotherapy), or if they had advanced or recurrent breast cancer (Group D). Results A total of 279 patients returned questionnaires (62, 79, 92 and 46 patients in Groups A, B, C and D, respectively). In adjuvant treatment groups, 43 patients (18.5%) quit their job during or after treatment. Most patients had quit their jobs at the time of diagnosis (7.5%), followed by those undergoing chemotherapy (5.6%) and those at the time of operation (4.9%). Quit rate from the workplace in which patients worked at the time of diagnosis was highest in Group C (30%), followed by Group B (20%) and Group A (13%). At the time of operation, 127 patients (57%) were absent from work. In Group D, 16 patients (35%) quit their job during treatment. Rates for patients currently working who had anxiety were 62, 30, 26 and 9% in Groups D, C, B and A, respectively. Conclusions In adjuvant treatment groups, in which quit rate was highest at the time of diagnosis, consultation about working is necessary immediately after diagnosis. Patients treated most heavily had higher quit rates and experienced more anxiety about working.

Abstract P2-01-09: Circulating tumor cells (CTCs) in the venous drainage of the breast in patients with primary breast cancer

Background: CTCs are shed from tumors and circulate in the peripheral blood after passing through the drainage vein. Axillary lymph node dissection (ALND) provides access to the lateral thoracic vein which flows directly into the axillary vein. In this preliminary study, we evaluated the feasibility of detecting CTCs in the peripheral blood and in the lateral thoracic venous blood for breast cancer patients who underwent ALND. Methods: From June 2016 to March 2017, breast cancer patients who underwent ALND in our institute were eligible for this study. A peripheral blood sample,10ml, was drawn just before the surgery or one day before the surgery. A lateral thoracic venous blood sample was taken from the resected breast just after resection. A blood sample of 0.2ml or more was necessary for CTC isolation. The CTCs in the peripheral blood before surgery (periCTC) and in the blood from the lateral thoracic vein of the resected breast (ltvCTC) were quantitatively examined by using a size-selective CTC isolation platform. Results: A total of 21 patients with median age 51 years (37-75) were enrolled to the study. Of the 21 patients, 38% were premenopausal, 52% had neoadjuvant chemotherapy. Fifty-seven percent were ER and/or PgR positive, 24% were HER2 positive. Fifty-seven percent were stage II disease and 43% were stage III. In 3 patients, we couldn9t obtain sufficient blood samples from the lateral thoracic vein. Of the remaining 18 patients, we were able to obtain the median 0.5ml (0.2-2.0) blood samples from the lateral thoracic vein. CTCs were detected in peripheral blood in 15 patients (71%) and median periCTC count was 1 CTC/10ml (0-39). In lateral thoracic venous blood, CTCs were detected in all patients who had sufficient blood samples and the median ltv CTC count was 35.5 CTC/ml (2.5-370). In 5 of 6 patients whom CTCs in peripheral blood samples were not detected, CTCs could be detected in the blood samples from lateral thoracic vein. Conclusion: CTCs can be detected in the peripheral blood and in the blood from lateral thoracic vein in patients with localized breast cancer, and can be detected at a higher rate and at a higher concentration in the blood from lateral thoracic vein than in peripheral blood. Citation Format: Hattori M, Nakanishi H, Yoshimura A, Adachi Y, Iwase M, Gondo N, Kotani H, Sawaki M, Yatabe Y, Iwata H. Circulating tumor cells (CTCs) in the venous drainage of the breast in patients with primary breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-01-09.

Correction to: Phase I dose-finding study of eribulin and capecitabine for metastatic breast cancer: JBCRG-18 cape study

The article “Phase I dose-finding study of eribulin and capecitabine for metastatic breast cancer: JBCRG-18 cape study”, written by Masaya Hattori, Hiroshi Ishiguro, Norikazu Masuda, Akiyo Yoshimura, Shoichiro Ohtani, Hiroyuki Yasojima, Satoshi Morita, Shinji Ohno, and Hiroji Iwata, was originally published electronically on the publisher’s Internet portal (currently SpringerLink) on 31 August 2017 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on [9 November 2017] to ©.

Comparison of sentinel lymph node biopsy between invasive lobular carcinoma and invasive ductal carcinoma

BackgroundRecent studies suggested that ALND (axillary lymph node dissection) can be avoided in breast cancer patients with limited SLN (sentinel lymph node) metastasis. However, these trials included only several invasive lobular carcinoma (ILC) cases, and the validity of omitting ALND for ILC remains controversial. Here, we examined whether omitting ALND is feasible in ILC treatment.MethodsA total of 3771 breast cancer patients underwent surgery for breast cancer at the Aichi Cancer Center Hospital between January 2006 and December 2015. We excluded patients with neoadjuvant therapy or without axillary management, and identified 184 ILC patients and 2402 invasive ductal carcinoma (IDC) patients. We compared SLN and non-SLN metastasis rates and the number of total ALN metastases between the ILC and IDC cohorts, and we examined the factors that influenced non-SLN metastasis in the SLN micrometastasis group.ResultsSLN biopsies were performed in 171 (93%) ILC and 2168 (90%) IDC cases, and 31 (18%) ILC and 457 (21%) IDC cases were SLN micrometastasis and macrometastasis (p = 0.36). Among SLN macrometastasis patients, 17 (68%) ILC cases and 163 (46%) IDC cases showed non-SLN metastasis (p = 0.03). The number of non-SLN metastases was greater in ILC cases compared with IDC cases. Multivariate analysis showed that ILC was the influential factor predicting non-SLN metastasis in patients with SLN macrometastasis.ConclusionILC cases had more non-SLN metastasis than IDC cases among SLN-positive cases, and ILC was an important factor for the prediction of non-SLN positivity in SLN macrometastasis cases. Omitting ALND for ILC with positive SLNs requires more consideration.

Abstract P6-01-04: Changes in Ki67 expression in breast cancer during the menstrual cycle and menopause

Background Previous studies have shown that the menstrual cycle phase can influence PgR status of breast cancer. But data on whether the menstrual cycle phase affects Ki67 expression is inconsistent. This study aims to compare the Ki67 expression on ultrasonography guided vacuum-assisted breast biopsy (US-guided VABB) with matched breast cancer surgical specimens. Materials and Methods In 120 breast cancer patients without neoadjuvant chemotherapy who underwent US-guided VABB and surgical resection from April 2008 and March 2012 at Aichi Cancer Center Hospital, we examined the concordance of Ki67 level between US-guided VABB and surgical specimen. All the US-guided VABB were performed using 11-gauge Mammotome. In this study, the Ki67 cut-off level for positivity was defined at 20%. Two phases of the menstrual cycle were pre-defined as indicated; phase 1 (low estrogen) days 27–35 or 1–6; phase 2 (high and intermediate estrogen) days 7–26 (Hayes BP, et al. Breast Cancer Res Treat 2013). We defined the three groups as follows: the non-matching menstrual phase group (different menstrual cycle phase at the time of biopsy and surgery: n=18), the matching menstrual phase group (same menstrual cycle phase at the time of biopsy and surgery: n=25), and the post-menstrual group (n=77). We evaluated the discordance of Ki67 expression between US-guided VABB and surgical specimens in the three groups. Results A differential expression of Ki67 was found in 13 patients and the concordance rate of Ki67 expression between US-guided VABB and surgical specimens was 89.2% with a Kappa statistic value of 0.78. (The concordance rate of ER, PgR, and HER2 status were 96.4%, 90.2%, and 97.0%, respectively.) There were no major differences in tumor and patient characteristics (age, pathological tumor size, and number of biopsy specimens) between the non-matching menstrual phase group and the matching menstrual phase group. The discordance rate of Ki67 expression for the non-matching menstrual phase group, the matching menstrual phase group, and the post-menstrual group were 22.2%, 4.0%, and 10.4%, respectively. In the patients with ER positive tumors, the discordance rate of Ki67 expression for the non-matching menstrual phase group, the matching menstrual phase group, and the post-menstrual group were 23.5%, 4.8%, and 10.9%, respectively. The discordance rate of Ki67 expression tended to be higher in the non-matching menstrual phase group than in the matching menstrual phase group. (p=0.11) Conclusions Though limited by the low number of patients, our study suggested that the menstrual cycle could affect Ki67 expression as patients with different menstrual cycle phase at the time of biopsy and surgery show discordant results. Prospective evaluation of Ki67 expression in premenopausal patients with ER positive tumor is needed. Citation Format: Takashi Fujita, Masataka Sawaki, Masaya Hattori, Naoto Kondo, Akiyo Yoshimura, Mari Ichikawa, Yayoi Adachi, Tomoka Hisada, Haruru Kotani, Junko Ishigro, Hiroji Iwata. Changes in Ki67 expression in breast cancer during the menstrual cycle and menopause [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-04.

Abstract P2-01-18: Preoperative axillary imaging with ultrasonography: Among the breast cancer patients with lymph node metastases, can we identify the patients who may omit axillary dissection?

(Introduction) ACOSOG Z11 and EORTC AMAROS showing little benefit to axillary dissection(ALND) for early stage breast cancers with limited nodal disease have led us to questioning the value of preoperative axillary imaging. It may not result in a benefit to the patients to perform ALND by diagnosing a few or small axillary lymph node(ALN) metastases preoperatively. (Aim) A purpose of this study is to determining the association between diagnostic method and metastatic number of ALN metastases, and to find the patients who can omit ALND safely even if with ALN metastases. (Methods)A database of consecutive primary breast cancer patients who underwent comlete ALND at our institution in 2008-2011 was analyzed. After we excluded patients treated with neoadjuvant systemic therapy, a total of 390 patients were included. By diagnostic methods of ALN metastases, we classified them in four groups as follows. Group A (n=41) : suspicious ALNs on axillary ultrasound(AUS) and ultrasound-guided fine needle aspiration cytology (FNAC) positive, Group B (n=47) : only one abnormal ALN on AUS +/- FNAC, Group C(n=53) : multiple abnormanl ALNs +/- FNAC, Group D (n=249) : negative ALNs on AUS but SLNB positive . (Results) The median number (range) of ALN metastases were 3(1-22) in GropuA, 2(0-12) in Group B, 7(1-37) in Group C, 1(1-17) in Group D. There were significant differences in number of metastases between Group A/B/C and Group D (p=.02, p=.01, p=.002). Paitents with 3 or less positive ALNs were 24.5% (13/53) in Group C, whereas 61.0% (25/41) in Group A and 68.1% (32/47) in Group B (p=.04, p=.02). We next evaluated the influence of patient- and tumour-related variables on the number of positive ALNs in Group A/B. Factors such as age, tumour size ( 20mm), ER status(positive vs negative), HER2 status (positive vs negative), nuclear grade (1/2 vs 3), menstruation status (pre vs post menopausal) were examined. However there were no significant differences in all factors between the patients with 4 or more ALN metastases and patients with 3 or less ALN metastases. As a result of multivariable analysis, relative risk (95%CI, p-value) of age was 0.92 (0.546-1.347, 0.84), tumour size : 0.82 (0.511-1.418, 0.76), ER status : 1.06 (0.873-1.821, 0.76), HER2 status : 1.17 (0.853-2.390, 0.28), nuclear grade : 0.43 (0.420-1.22, 0.34), menstruation status : 0.85 (0.538-1.693, 0.89). (Conclusion) In our contemporary series, patients diagnosed as ALN metastases preoperatively have significantly more involved nodes compared to SLNB positive patients regardless of the diagnostic method, suggesting that such patients should proceed to ALND. Preoperative axillary imaging are useful to identify node-positive breast cancer patients requiring ALND . Citation Format: Naoto Kondo, Takashi Fujita, Masataka Sawaki, Masaya Hattori, Akiyo Yoshimura, Mari Ichikawa, Junko Ishiguro, Yayoi Adachi, Haruru Kotani, Tomoka Hisada, Hiroji Iwata. Preoperative axillary imaging with ultrasonography: Among the breast cancer patients with lymph node metastases, can we identify the patients who may omit axillary dissection? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-18.