Kotaro Iijima

Malignant transformation of breast fibroadenoma to malignant phyllodes tumor: long-term outcome of 36 malignant phyllodes tumors

BackgroundMalignant phyllodes tumor of the breast is a rare neoplasm for which clinical findings remain insufficient for determination of optimal management. We examined the clinical behavior of these lesions in an attempt to determine appropriate management. We evaluated long-term outcome and clinical characteristics of malignant phyllodes tumors arising from fibroadenomas of the breast.MethodsA total of 173 patients were given a diagnosis of phyllodes tumor and underwent surgery at the Cancer Institute Hospital in Japan between January 1980 and December 1999. Of these patients, 39 (22.5%) were given a diagnosis of malignant phyllodes tumor; in three of these cases, detailed medical records were lost. Malignant phyllodes tumors were classified into two groups based on history of malignant transformation. Of the 36 malignant cases, 11 (30.6%) were primary and were given a diagnosis of fibroadenoma, experienced recurrence during the follow-up period, and were diagnosed with malignant phyllodes tumor (cases with a history of fibroadenoma). The other group was defined as cases without history of fibroadenoma and in whom lesions initially occurred as malignant phyllodes tumors. Based on differences between the two groups, overall survival curves were plotted using the Kaplan–Meier method, and statistical comparisons were performed using the log-rank test and Peto and Peto’s test.ResultsThe outcome of cases with history of fibroadenoma was significantly better than that of cases without history of fibroadenoma.ConclusionsPatients with malignant phyllodes tumors but without prior history of malignant transformation who exhibit rapid growth within 6xa0months require aggressive treatment.

Ductal carcinoma in situ and sentinel lymph node metastasis in breast cancer

BackgroundThe impact of sentinel lymph node biopsy on breast cancer mimicking ductal carcinoma in situ (DCIS) is a matter of debate.MethodsWe studied the rate of occurrence of sentinel lymph node metastasis in 255 breast cancer patients with pure DCIS showing no invasive components on routine pathological examination. We compared this to the rate of occurrence in 177 patients with predominant intraductal-component (IDC) breast cancers containing invasive foci equal to or less than 0.5 cm in size.ResultsMost of the clinical and pathological baseline characteristics were the same between the two groups. However, peritumoral lymphatic permeation occurred less often in the pure DCIS group than in the IDC-predominant invasive-lesion group (1.2% vs. 6.8%, p = 0.002). One patient (0.39%) with pure DCIS had two sentinel lymph nodes positive for metastasis. This rate was significantly lower than that in patients with IDC-predominant invasive lesions (6.2%; p < 0.001).ConclusionsBecause the rate of sentinel lymph node metastasis in pure DCIS is very low, sentinel lymph node biopsy can safely be omitted.

P106 Incidence of chemotherapy-induced amenorrhea in pre-menopausal patients with breast cancer following adjuvant anthracycline and taxane

Background nThe purpose of this study was to determine the incidence of amenorrhea among breast cancer patients aged 40 years and younger following adjuvant chemotherapy.

Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

PURPOSEnThe indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status.nnnMETHODS AND MATERIALSnRetrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status.nnnRESULTSnMultivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295).nnnCONCLUSIONnAmong postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.

Changes in Tumor Expression of HER2 and Hormone Receptors Status after Neoadjuvant Chemotherapy in 21,755 Patients from the Japanese Breast Cancer Registry

BACKGROUNDnWe investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data.nnnPATIENTS AND METHODSnRecords of more than 300,000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21,755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization.nnnRESULTSnpCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10,973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward.nnnCONCLUSIONnWe confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.

Incidence of chemotherapy-induced amenorrhea in premenopausal patients with breast cancer following adjuvant anthracycline and taxane

BackgroundThe purpose of this study was to determine the incidence of amenorrhea among breast cancer patients aged 40xa0years and younger following adjuvant chemotherapy.MethodsA follow-up questionnaire survey was conducted with premenopausal women with breast cancer who were treated with adjuvant anthracycline and taxane-based chemotherapy.ResultsIn total, 66 women were retrospectively reviewed. Forty-nine patients were treated with a regimen containing anthracycline followed by taxane and 17 patients with anthracycline alone. Fifty-eight patients (87.9%) experienced amenorrhea during chemotherapy; 14 patients (21.2%) had persistent amenorrhea after chemotherapy. The incidence of amenorrhea during chemotherapy and persistent amenorrhea was higher in patients older than 36 than in younger patients (97.9 vs. 63.2%, 27.7 vs. 5.3%). Additional taxane resulted in a higher incidence of amenorrhea compared with anthracycline-containing regimen alone (93.9 vs. 70.6%). Multivariate analysis showed that age (≥36xa0years) was independently associated with the incidences of amenorrhea during chemotherapy (pxa0=xa00.007).ConclusionAge was the strongest predictor of the incidence of amenorrhea during chemotherapy. It is unclear whether additional taxane may contribute to amenorrhea. This information could be useful in deciding whether to use adjuvant chemotherapy.

Validation study of the UICC TNM classification of malignant tumors, seventh edition, in breast cancer.

BackgroundThe TNM classification of the Unio Internationalis Contra Cancrum was revised for the seventh edition. The major change concerning breast cancer is a change in the stages for patients with T0 or T1N1miM0. In the present study, the seventh edition of the TNM classification was validated in breast cancer.MethodsThe stages of 416 breast cancer patients, treated at our hospital in 1996, were classified according to the TNM classification, sixth and seventh editions, and their prognoses were compared.ResultsCase distribution using the sixth edition was stage 0, 56 cases (13.5xa0%); stage I, 158 cases (38.0xa0%); stage II, 130 [A, 102; B, 28] cases (31.2 [A, 24.5; B, 6.7]xa0%); and stage III, 72 [A, 31; B, 8; C, 33] cases (17.3 [A, 7.5; B, 1.9; C, 7.9]xa0%). According to the seventh edition, the stages for 20 patients, accounting for 19.6xa0% of IIA cases according to the sixth edition, decreased from IIA to IB. The 10-year overall survivals were stage 0, 91.1xa0%; stage I, 88.6xa0%; stage II, 80.8xa0%; and stage III, 63.9xa0% according to the sixth edition; and stage 0, 91.1xa0%; stage I, 88.8xa0%; stage II, 79.1xa0%; and stage III, 63.9xa0% according to the seventh edition. Although no significant differences were seen among the survival rates for stages 0 to II according to the sixth edition, there was a significant difference between stage I and II according to the seventh edition (pxa0=xa00.026).ConclusionThe latest revision of the TNM classification is appropriate for breast cancer from the perspective of prognosis.

Histogenesis of metaplastic breast carcinoma and axillary nodal metastases

A 40‐year‐old breast‐feeding woman presented with left breast swelling. On physical examination a 7u2003cm mass was found in the breast. Because biopsy demonstrated malignant tissue, mastectomy with axillary nodal dissection was performed. Pathological findings were consistent with metaplastic breast carcinoma with nodal metastases. The primary tumor consisted of three types of invasion: ductal, squamous, and sarcomatous. Furthermore, three morphological transitions were observed: ductal–squamous, ductal–sarcomatous, and squamous–sarcomatous. Ductal–squamous (12/18 microscopy slides) and squamous–sarcomatous transitions (10/18) were more commonly observed than ductal–sarcomatous transition (3/18). Furthermore, immunohistochemistry showed loss of epithelial marker (cytokeratin) and acquisition of mesenchymal markers (vimentin and α‐smooth muscle actin) in the sarcomatous component. These findings suggested that epithelial–mesenchymal transition had occurred in the tumor and that two pathways, ductal–squamous–sarcomatous and ductal–sarcomatous transition, were involved in progression of metaplastic breast carcinoma. The main pathway appeared to be ductal–squamous–sarcomatous transition. Regarding the nodal metastases, of 13 positive nodes, ductal, squamous, and sarcomatous components were observed in 13, seven, and two nodes, respectively. Moreover, as in the primary tumor, ductal–squamous and squamous–sarcomatous transitions were observed. This suggested that the ductal component metastasized to the nodes and that epithelial–mesenchymal transition subsequently occurred within the nodes.

Optimal surveillance for postoperative metastasis in breast cancer patients.

PurposeTo establish an optimal surveillance schedule after surgery for breast cancer, patients included in an institutional database were retrospectively investigated with respect to the first metastatic site and timing of recurrence.Patients and methodsWe investigated 11,676 pT1-4pN0-2M0 breast cancer patients treated from 1985 to 2009 and followed up until June 2014. Our surveillance protocol included physician visits and examinations with bone scans, liver echography, chest roentgenography and laboratory tests. We evaluated the liver, bones, lungs and pleura as surveillance covering sites (SCS) in addition to parameters such as time points exceeding 80xa0% with respect to the accumulated percentage of patients of recurrence and the number of surveillance per one recurrence (NSR), calculated by dividing the number of patients at risk of recurrence at the start of a particular time frame by the number of patients of recurrence at SCS within that period.ResultsThere were a total of 1,962 recurrent patients, including 601 patients with locoregional recurrence, nine patients with recurrence in the opposite breast, 1,349 patients with recurrence at distant sites and three unknown patients. The number of patients with the bones, lungs, liver and pleura as the first site of recurrence was 447, 324, 144 and 69, respectively, and 72.9xa0% of the distant metastatic lesions belonged to SCS. The five-year overall survival rate after recurrence among the patients with single recurrent site was longer than that observed among the patients with multiple sites of recurrence (43.3 vs 25.3xa0%; pxa0<xa00.0001). In addition, more than 80xa0% of the patients of liver metastasis were detected within 5xa0years after surgery, while 80xa0% of the patients of pleura metastasis were detected within 10xa0years. The NSR was below 200 for the 10-year period, as was the NSR of the patients with lymph node metastasis and a positive hormone receptor status. In contrast, the NSR of the patients with a negative hormone receptor status was above 200 after 5xa0years.ConclusionsIn this study, the prognosis of the patients with a single site of recurrence was superior to that of the patients with multiple sites. Curable patients with distant metastases included those with single metastatic sites. The optimal surveillance schedule should be established taking into consideration that the incidence of metastasis differs among metastatic sites during follow-up.

Body mass index and survival after diagnosis of invasive breast cancer: a study based on the Japanese National Clinical Database—Breast Cancer Registry

Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed‐up for a median period of 6.7 years entered in the National Clinical Database–Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m2) categories; <18.5 (underweight), ≥18.5–<21.8 (reference), ≥21.8–<25, ≥25–<30 (overweight), and ≥30 (obese). We divided normal weight patients into two subgroups because this category includes many patients compared to others. The timing of BMI measurement was not specified. The Cox proportional hazards model and cubic spline regression were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Smoking, alcohol, and physical activity were not controlled. A total of 1418 all‐cause, 937 breast cancer–specific deaths, and 2433 recurrences were observed. Obesity was associated with an increased risk of all‐cause (HR: 1.46; 95% CI: 1.16–1.83) and breast cancer–specific death (HR: 1.47; 95% CI: 1.11–1.93) for all patients, and with all‐cause (HR: 1.47; 95% CI: 1.13–1.92) and breast cancer–specific death (HR: 1.58; 95% CI: 1.13–2.20) for postmenopausal patients. Being underweight was associated with an increased risk of all‐cause death for all (HR: 1.41; 95% CI: 1.16–1.71) and for postmenopausal patients (HR: 1.45; 95% CI: 1.15–1.84). With regard to subtype and menopausal status, obesity was associated with an increased risk of breast cancer–specific death for all cases of luminal B tumor (HR: 2.59; 95% CI: 1.51–4.43; Pheterogeneity of Luminal B vs. Triple negative = 0.016) and for postmenopausal patients with luminal B tumor (HR: 3.24; 95% CI: 1.71–6.17). Being obese or underweight is associated with a higher risk of death among female breast cancer patients in Japan.