How pregnancy and childbirth affect the working conditions and careers of women surgeons in Japan: findings of a nationwide survey conducted by the Japan Surgical Society.

PURPOSE: To identify the conflicts between a career as a surgeon and pregnancy and childbirth for women in Japan. METHODS: The Japan Surgical Society conducted a nationwide survey on pregnancy and childbirth among its members who are women. The questionnaire included items regarding demography, working styles, and pregnancy and childbirth, including adverse events and harassment. RESULTS: The response rate was 29.9% (1068 responses, median age, 37 years). Among the responders, 61% were married and 47% had children (average number of children, 1.7). Half of the respondents reported having experienced sexual harassment and 62% reported having received unwelcome comments about pregnancy. About 20% had undergone fertility treatment. In total, 51% had pregnancies, with miscarriages in 33% of these. The top answer for the best timing for pregnancy and childbirth was after becoming board-certified. Nearly one-third of first-time mothers experienced adverse events during pregnancy and delivery, and 28% quit or changed their job because of their pregnancy and the birth of their first child. CONCLUSIONS: Japanese women who choose a career as a surgeon face obstacles during pregnancy and childbirth. It is vital to share the findings of this study and understand the issues associated with pregnancy and childbirth regardless of gender. Interventions are essential to ensure that every pregnant surgeon has a safe working environment to allow unobstructed development of her career.

Mentorship as Experienced by Women Surgeons in Japan.

BACKGROUND: Women have accounted for over 30% of new medical students since 1995 in Japan. Establishing support systems for women surgeons to continue their work is a major issue in Japan. Mentorship can be one of the most effective means to help women surgeons to continue their work. The purpose of this study was to clarify the current status of mentorship among Japanese women surgeons and to discuss the role of mentors for women surgeons. METHODS: Invitation letters were sent to all female members of the Japan Association of Women Surgeons in April 2011. An 84-item questionnaire survey was sent to those who agreed to participate in this study via the internet. RESULTS: Fifty-five surgeons participated in this study, a response rate of 48.7%. Sixty-seven percent of respondents found it difficult to continue in their job; 85% thought mentorship was necessary for women surgeons to progress in their careers; and 84% reported that they already had a mentor. Respondents thought that a mentor helped them to advance their clinical career, to stay in their job, and to provide moral support. However, mentors appeared to be less useful in helping them to advance their research career, to network, to increase their status, and to achieve a work-life balance. CONCLUSIONS: This study revealed areas where mentors appeared to be less helpful to women surgeons. The survey gave an indication of how to help improve and develop the career and personal life of women surgeons in Japan.

[DEVELOPMENTS IN BREAST IMAGING].

Breast cancer is the most frequent cancer in Japanese women. As breast density increases, the detection rate of breast cancer by mammography (MMG) decreases. Breast density notification laws have been enacted in several states in the USA. Supplemental screening tools for women with dense breasts are needed. The results of a large randomized trial to compare the sensitivity, specificity, and cancer detection rate of MMG and adjunctive ultrasonography (US) to screen for breast cancer in Japan (J-START) were reported last year. More than 70,000 women aged 40 to 49 years were enrolled. The sensitivity and cancer detection rate were significantly higher in the MMG+US group than in the MMG-alone group. Automated breast ultrasonography is a tool to overcome the operator dependency of hand-held US and low reproducibility. Digital breast tomosynthesis, referred to as 3D MMG, offers higher sensitivity and specificity than MMG. Contrast-enhanced spectral MMG is an MMG scan using contrast medium to detect breast cancer more clearly even in dense breasts. It is often used for women at high risk for cancer and substituted for magnetic resonance imaging. A dedicated breast positron-emission tomography (PET) system has been available in Japan with insurance coverage since 2013. More cases of cancer were detected using breast PET than whole-body PET. Additional studies including mortality rates are needed.

Utility of intraoperative frozen section examinations of surgical margins: implication of margin-exposed tumor component features on further surgical treatment.

OBJECTIVE: In patients who underwent breast-conserving surgery, we attempted to identify the histological characteristics of margin-exposed tumor components on intraoperative frozen section examinations that were predictive of residual tumor components in additionally resected specimens. METHODS: Of 1835 patients who underwent breast-conserving surgery, we identified 220 patients who had positive surgical margins determined by intraoperative frozen section examinations and who had undergone immediate additional resections. Two observers (M.K., H.T.) reviewed the slides of frozen sections and confirmed the presence of tumor components. RESULTS: In additionally resected specimens, residual tumors were detected in 115 cases (52.3%) but not in 105 cases (47.7%). The primary tumor characteristics of extensive intraductal component (+), younger age, invasive lobular carcinoma and pathological T3 classification were significantly associated with the residual tumor components. The margin-exposed tumor components of the maximum diameter, number of positive margins and histological type were correlated with the residual tumors. Multivariate analysis showed that the maximum tumor diameter was an independent risk factor for residual tumors. CONCLUSIONS: Diagnosis of positive margins by intraoperative frozen section examinations was useful for predicting residual tumors, and three histological properties of the margin-exposed tumor components were correlated with the status of residual tumor components. Although it was impossible to clearly identify the single main factor for predicting patients for whom additional resections were not necessary, it may be possible to consider stratification of additional surgical therapy according to the characteristics of margin-exposed tumor components on intraoperative frozen section examinations.

The expression and clinical significance of ribophorin II (RPN2) in human breast cancer.

Ribophorin II (RPN2), part of the N-oligosaccharyltransferase complex, is highly expressed in breast cancer stem cells and is associated with tumor metastasis through interaction with mutant p53. The clinicopathological implication of RPN2 expression is undetermined. We examined immunohistochemically the expression levels of RPN2 and p53 in primary breast cancer tissues surgically resected from 218 patients. The correlations of RPN2 expression with the intrinsic subtype defined by hormone receptors (HRs) and HER2, clinicopathological parameters, p53 expression, and patients' clinical outcomes were examined. RPN2 was positive in 139 (64%), and the incidence of RPN2 expression was higher in the triple-negative breast cancer (TNBC) (HR-/HER2-) (65%) and HER2-enriched (HR-/HER2+) subtype (95%) than in the luminal A-like (HR+/HER2-) subtype (58%) (P = 0.0009). RPN2 expression was also correlated with p53 nuclear accumulation (P = 0.04). The RPN2-positive/p53-positive patient group showed significantly poorer prognosis than the RPN2-negative group for disease-free survival (P = 0.05) and for overall survival (P = 0.02). By multivariate analyses, the combination of RPN2 and p53 was not an independent prognostic factor. RPN2 expression was correlated with clinically aggressive features of breast cancer. These data support the further clinical application of anti-RPN2 therapy and the development of personalized medicine.

p53 expression in pretreatment specimen predicts response to neoadjuvant chemotherapy including anthracycline and taxane in patients with primary breast cancer.

While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB) are needed to predict neoadjuvant chemotherapy (NAC) response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane) at the National Cancer Center Hospital (NCCH). We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR) and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD). In a comparison between the 9 (5%) sensitive patients and 30 (16%) insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p＝0.045) and histological grade 3 (p＝0.011) were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC.

A prospective analysis of two studies that used the 5-mm interval slices and 5-mm margin-free method for ipsilateral breast tumor recurrence after breast-conserving surgery without radiotherapy.

BACKGROUND: Breast-conserving surgery with radiotherapy is one of standard treatments for early breast cancer. However, it is regarded as an option to treat elderly patients with small hormone receptor-positive breast cancer with breast-conserving surgery and hormone therapy without radiotherapy. We conducted two sequential prospective studies to examine the feasibility of breast-conserving surgery without radiotherapy since 2002 and present the results. PATIENTS AND METHODS: Primary female breast cancer patients who fulfilled the strict eligibility criteria were prospectively enrolled in two sequential studies named WORTH 1 and 2. The surgical materials were sliced in 5-mm intervals and all slices were examined microscopically. Postoperative radiotherapy was not allowed, but tamoxifen or anastrozole was administered for 5 years. Ipsilateral breast tumor recurrence (IBTR)-free survival was the primary outcome. RESULTS: The data of the two studies were combined (N = 321). The median follow-up period for IBTR was 94 months (4-192 months). Only three patients were treated with adjuvant chemotherapy. The 5- and 10-year IBTR-free rates were 97.0% and 90.5%, respectively. The age at operation and PR status affected IBTR rates independently. When we calculated IBTR-free rates of patients who were 65 years of age or older at the time of surgery and had PR-positive tumors, the 5- and 10-year IBTR rates were both 98.4%. CONCLUSIONS:  Our "5-mm-thick slice and 5-mm free-margin" method may be effective to select patients who can be treated by breast-conserving surgery and hormone therapy without radiotherapy.

Comparative study of the value of dual tracer PET/CT in evaluating breast cancer.

The present study was conducted to assess the relationship between tumor uptake and pathologic findings using dual-tracer PET/computed tomography (CT) in patients with breast cancer. Seventy-four patients with breast cancer (mean age 54 years) who underwent (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)F-FDG) PET/CT prior to surgery on the same day were enrolled in the present study. Images were reviewed by a board-certified radiologist and two nuclear medicine specialists who were unaware of any clinical information and a consensus was reached. Uptake patterns and measurements of dual tracers were compared with the pathologic findings of resected specimens as the reference standard. Mean (±SD) tumor size was 5.9 ± 3.2 cm. All primary tumors were identified on (18)F-FDG PET/CT and (11)C-choline PET/CT. However, (18)F-FDG PET/CT demonstrated focal uptake of the primary tumor with (n = 38; 51%) or without (n = 36; 49%) diffuse background breast uptake. Of the pathologic findings, multiple logistic regression analysis revealed an independent association between fibrocystic change and diffuse background breast uptake (odds ratio [OR] 8.57; 95% confidence interval [CI] 2.86-25.66; P < 0.0001). Tumors with higher histologic grade, nuclear grade, structural grade, nuclear atypia, and mitosis had significantly higher maximum standardized uptake values (SUV(max)) and tumor-to-background ratios (TBR) for both tracers. Multiple logistic regression analysis revealed that only the degree of mitosis was independently associated with a high SUV(max) (OR 7.45; 95%CI 2.21-25.11; P = 0.001) and a high TBR (OR 5.41; 95%CI 1.13-25.96; P = 0.035) of (11)C-choline PET/CT. In conclusion, (11)C-choline may improve tumor delineation and reflect tumor aggressiveness on PET/CT in patients with breast cancer.

Ipsilateral breast tumor recurrence (IBTR) in patients with operable breast cancer who undergo breast-conserving treatment after receiving neoadjuvant chemotherapy: risk factors of IBTR and validation of the MD Anderson Prognostic Index.

BACKGROUND: There is limited information about the risk factors for ipsilateral breast tumor recurrence (IBTR) after patients undergo breast-conserving surgery plus radiotherapy (breast-conserving treatment [BCT]) subsequent to neoadjuvant chemotherapy (NAC). The objective of the current study was to analyze these risk factors. METHODS: The authors collected data from 375 patients who underwent BCT and received NAC and analyzed the risk of IBTR associated with undergoing BCT after NAC. The usefulness of the MD Anderson Prognostic Index (MDAPI) for IBTR also was validated using the current data set. RESULTS: The median follow-up was 47.8 months, and the 4-year IBTR-free survival rate was 95.6%. Multivariate analysis demonstrated that estrogen receptor (ER) status and multifocality of the residual tumor were associated significantly with IBTR-free survival. In addition, patients who had ER-positive and human epidermal growth factor 2 (HER2)-negative tumors did not develop IBTR during the observation period. Although prognostic stratification according to MDAPI was relatively good for the prediction of IBTR in the study patients, the IBTR rate in the high-risk group was not very high and was lower than that in the intermediate-risk group. Multivariate analyses demonstrated that IBTR was an independent predictive factor for overall survival. CONCLUSIONS: ER status and multifocality of the residual tumor after NAC were independent predictors of IBTR after BCT. The MDAPI was barely adaptable to the study patients in terms of predicting IBTR. Patients with ER-positive and HER2-negative tumors had a favorable prognosis, whereas patients who developed IBTR after NAC had significantly worse overall survival. The authors propose a new IBTR prognostic index using the 2 factors that were identified as predictive of IBTR: ER status and multifocality of the residual tumor.

Evaluation of the usefulness of breast CT imaging in delineating tumor extent and guiding surgical management: a prospective multi-institutional study.

OBJECTIVE: The aim of the present study was to evaluate the usefulness of computed tomographic (CT) imaging in delineating tumor extent and guiding surgical management. BACKGROUND: The routine use of preoperative magnetic resonance imaging (MRI) is a controversial issue in breast cancer management. Negative studies with regard to the utility of MRI might be due to differences in positioning during imaging and subsequent surgery. METHODS: Candidates for breast-conserving surgery were eligible for the study. The surgeons marked the line of planned excision on the skin, which was also recorded on the CT image. Contrast-enhanced breast CT was performed in the supine surgical position. The CT results were used to help determine the extent of resection. The pathological findings were then compared with the CT-guided surgical plans. RESULTS: A total of 297 patients were involved. The surgeons widened the extent of resection in 42 (14.1%, 95% confidence interval 10.1%-18.1%) patients on the basis of the CT findings. Among the 6 patients whose procedures were changed to mastectomy, 4 had pathologically multicentric tumors and 2 had widely spread intraductal components. The remaining 36 patients underwent quadrantectomy instead of wide excision on the basis of the CT images. There were 3 patients in whom conversion from wide excision to quadrantectomy resulted in overexcision. Preoperative breast CT may have reduced the positive margin rate and also correctly changed the extent of surgery in 13.1% of patients. CONCLUSIONS: This prospective study suggests that breast CT, carried out in the supine position, is useful in the preoperative determination of the optimal surgical procedure.

Identifying ductal carcinoma in situ cases not requiring surgery to exclude postoperative upgrade to invasive ductal carcinoma.

BACKGROUND: Prospective cohort studies are being conducted worldwide to identify a low-grade group of ductal carcinoma in situ (DCIS) that does not require surgery. However, to do this, it is necessary to predict which cases, diagnosed with preoperative DCIS, will be upgraded to invasive ductal carcinoma (IDC) after surgery. METHODS: In this study, we evaluated the frequency of IDC upgrades in patients who were preoperatively diagnosed with DCIS at Showa University using the criteria of ongoing clinical trials. We divided our cases into those that could be enrolled in the ongoing trial and those that could not. Moreover, we evaluated whether CNB, which is allowed only in Japanese clinical trials, is related to the IDC mixture. RESULTS: There were 211 (52.1%) cases that matched the criteria of the U.K. and Netherlands trials, of which 62 (29.4%) were upgraded to IDC. A total of 113 (27.9%) cases met the criteria for clinical trials in Japan and the U.S., 25 (22.1%) of which were upgraded to IDC and 47 (34.6%) which matched when considering biopsy methods. The number of cases upgraded to IDC decreased to four (8.5%). CONCLUSIONS: This study demonstrated that there were a certain number of mixed IDC. We will pay attention to the results of ongoing clinical trials regarding how the presence of this mixed IDC affects the prognosis in non-surgery cases. Careful follow-up is recommended for non-surgical treatment.

Diagnostic performance of dedicated breast positron emission tomography.

BACKGROUND: Dedicated breast positron emission tomography (dbPET) has been developed for detecting smaller breast cancer. We investigated the diagnostic performance of dbPET in patients with known breast cancer. METHODS: Eighty-two preoperative patients with breast cancer were included in the study (84 tumours: 11 ductal carcinomas in situ [DCIS], 73 invasive cancers). They underwent mammography (MMG), ultrasonography (US), and contrast-enhanced breast magnetic resonance imaging (MRI) before whole-body PET/MRI (WBPET/MRI) and dbPET. We evaluated the sensitivity of all modalities, and the association between the maximum standard uptake value (SUVmax) level and histopathological features. RESULTS: The sensitivities of MMG, US, MRI, WBPET/MRI and dbPET for all tumours were 81.2% (65/80), 98.8% (83/84), 98.6% (73/74), 86.9% (73/84), and 89.2% (75/84), respectively. For 11 DCIS and 22 small invasive cancers (≤ 2 cm), the sensitivity of dbPET (84.9%) tended to be higher than that of WBPET/MRI (69.7%) (p = 0.095). Seven tumours were detected by dbPET only, but not by WBPET/MRI. Five tumours were detected by only WBPET/MRI because of the blind area of dbPET detector, requiring a wider field of view. After making the mat of dbPET detector thinner, all 22 scanned tumours were depicted. The higher SUVmax of dbPET was significantly related to the negative oestrogen receptor status, higher nuclear grade, and higher Ki67 (p < 0.001). CONCLUSIONS: The sensitivity of dbPET for early breast cancer was higher than that of WBPET/MRI. High SUVmax was related to aggressive features of tumours. Moreover, dbPET can be used for the diagnosis and oncological evaluation of breast cancer.

Up-regulation of PSF1 promotes the growth of breast cancer cells.

PSF1 is a subunit of the GINS complex that functions along with the MCM2-7 complex and Cdc45 in eukaryotic DNA replication. Although mammalian PSF1 is predominantly expressed in highly proliferating cells and organs, little is known about the roles of PSF1 in mature cells or cancer cells. We found that PSF1 was expressed at relatively high levels in breast tumor cells, but at low levels in normal breast cells. Knockdown of PSF1 expression using small interfering RNA (siRNA) slowed the growth of breast cancer cell lines by delaying DNA replication but did not affect proliferation of normal human mammary epithelial cells. Reduced PSF1 expression also inhibited anchorage-independent growth in breast cancer cell lines. These results suggest that PSF1 over-expression is specifically involved in breast cancer cell growth. Therefore, PSF1 inhibition might provide new therapeutic approaches for breast cancer.

Prognostic factors in young Japanese women with breast cancer: prognostic value of age at diagnosis.

OBJECTIVE: The primary objective of this study was to verify whether breast cancer patients aged <35 at diagnosis have poorer prognoses than those aged 35-39, in other words, to identify the prognostic value of age in younger premenopausal patients under 40 years old. The secondary objective was to assess prognostic factors specific for younger premenopausal patients. METHODS: We identified 242 consecutive patients who were diagnosed with stage I-III breast cancer before the age of 40 and underwent surgery between 1990 and 2004. We compared disease-free survival and overall survival in patients aged <35 years and those aged 35-39 years, and evaluated clinicopathological factors associated with disease-free survival or overall survival in each age group and in all patients under the age of 40. RESULTS: Ninety-nine (41%) patients were younger than 35 years and 143 (59%) were between 35 and 39 years. No significant difference in disease-free survival or overall survival was found between the two groups. In our cohort of patients under the age of 40, the independent factors associated with poor disease-free survival and overall survival included positive axillary lymph nodes and triple-negative status, but not age at diagnosis. Adverse prognostic factors also did not differ considerably between the two age groups. CONCLUSIONS: Age at diagnosis was not an independent prognostic factor in our study. Our findings suggest that other clinicopathological features rather than age should be used to determine individualized treatment courses for breast cancer patients younger than 40 years.

A Retrospective Analysis of the Relationship Between the Result of BRCA1/2 Genetic Testing and Surgical Method Selection in Japan.

BACKGROUND: We studied the extent of BRCA1/2 genetic testing to help select the surgical approach for patients with breast cancer in Japan remains unclear. PATIENTS AND METHODS: The study subjects were female patients with primary unilateral invasive breast cancer considered as candidates for breast-conserving surgery who underwent preoperative BRCA1/2 genetic testing. A retrospective analysis was performed on the results of BRCA1/2 genetic testing and surgical method selection using national registration data from the Japanese Hereditary Breast and Ovarian Cancer Syndrome Consortium. RESULTS: Our study included 318 female patients. Among these patients, 23.7% of patients with BRCA1/2 mutations and 61.8% of patients without these variants underwent breast-conserving surgery (P < .01). Among the patients with BRCA1/2 mutations, those who chose breast-conserving surgery tended not to undergo risk-reducing salpingo-oophorectomy (P < .05). Among the patients with BRCA1/2 mutations who underwent mastectomy for the affected side, 31.8% received contralateral risk-reducing mastectomy. Patients diagnosed with breast cancer under the age of 50 years were more likely to have contralateral risk-reducing mastectomy than patients over the age 50 years (P < .05). CONCLUSIONS: Patients with BRCA1/2 mutations tend to choose mastectomy. However, it is speculated that the final surgical method selection is made in consideration of not only the test results but also with careful consideration of the patient, taking into account other factors including individual values for risk-reducing surgeries and the age of breast cancer onset.

Optimal Breast Density Characterization Using a Three-Dimensional Automated Breast Densitometry System.

Dense breasts are a risk factor for breast cancer. Assessment of breast density is important and radiologist-dependent. We objectively measured mammographic density using the three-dimensional automatic mammographic density measurement device Volpara™ and examined the criteria for combined use of ultrasonography (US). Of 1227 patients who underwent primary breast cancer surgery between January 2019 and April 2021 at our hospital, 441 were included. A case series study was conducted based on patient age, diagnostic accuracy, effects of mammography (MMG) combined with US, size of invasion, and calcifications. The mean density of both breasts according to the Volpara Density Grade (VDG) was 0-3.4% in 2 patients, 3.5-7.4% in 55 patients, 7.5-15.4% in 173 patients, and ≥15.5% in 211 patients. Breast density tended to be higher in younger patients. Diagnostic accuracy of MMG tended to decrease with increasing breast density. US detection rates were not associated with VDG on MMG and were favorable at all densities. The risk of a non-detected result was high in patients without malignant suspicious calcifications. Supplementary use of US for patients without suspicious calcifications on MMG and high breast density, particularly ≥25.5%, could improve the breast cancer detection rate.

Magnetically Guided Localization Using a Guiding-Marker System® and a Handheld Magnetic Probe for Nonpalpable Breast Lesions: A Multicenter Feasibility Study in Japan.

Accurate pre-operative localization of nonpalpable lesions plays a pivotal role in guiding breast-conserving surgery (BCS). In this multicenter feasibility study, nonpalpable breast lesions were localized using a handheld magnetic probe (TAKUMI) and a magnetic marker (Guiding-Marker System®). The magnetic marker was preoperatively placed within the target lesion under ultrasound or stereo-guidance. Additionally, a dye was injected subcutaneously to indicate the extent of the tumor excision. Surgeons checked for the marker within the lesion using a magnetic probe. The magnetic probe could detect the guiding marker and accurately localize the target lesion intraoperatively. All patients with breast cancer underwent wide excision with a safety margin of ≥5 mm. The presence of the guiding-marker within the resected specimen was the primary outcome and the pathological margin status and re-excision rate were the secondary outcomes. Eighty-seven patients with nonpalpable lesions who underwent BCS, from January to March of 2019 and from January to July of 2020, were recruited. The magnetic marker was detected in all resected specimens. The surgical margin was positive only in 5/82 (6.1%) patients; these patients underwent re-excision. This feasibility study demonstrated that the magnetic guiding localization system is useful for the detection and excision of nonpalpable breast lesions.

p53 expression in tumor-stromal fibroblasts forming and not forming fibrotic foci in invasive ductal carcinoma of the breast.

The purpose of this study was to determine whether p53 protein expression in tumor-stromal fibroblasts forming fibrotic foci is a significant outcome predictor, similar to p53 protein expression in tumor-stromal fibroblasts not forming fibrotic foci, and whether the combined assessment of p53 expression in tumor-stromal fibroblasts forming and not forming fibrotic foci served as an important outcome predictor among 1039 patients with invasive ductal carcinoma of the breast. We analyzed the outcome predictive power of the Allred score risk classification for p53 in tumor-stromal fibroblasts forming and not forming fibrotic foci using multivariate analyses with well-known clinicopathological factors. The Allred score risk classifications for p53 in tumor-stromal fibroblasts forming and not forming fibrotic foci were superior to the Allred scores for p53 in tumor-stromal fibroblasts not forming fibrotic foci alone for accurately predicting the tumor-related death of patients with invasive ductal carcinoma when examined using multivariate analyses. The Allred score risk classification for p53 in tumor-stromal fibroblasts forming and not forming fibrotic foci significantly increased the hazard rates for tumor recurrence and tumor-related death independent of the UICC pTNM stage in the multivariate analyses. These results indicated that the Allred score risk classification based on the combined assessment of p53 expression in tumor-stromal fibroblasts forming and not forming fibrotic foci is a very useful outcome predictor among patients with invasive ductal carcinoma.

Grading system for lymph vessel tumor emboli: significant outcome predictor for patients with invasive ductal carcinoma of the breast who received neoadjuvant therapy.

The purpose of this study was to confirm that the grades of lymph vessel tumor emboli in biopsy specimens obtained before neoadjuvant therapy and in the surgical specimens obtained after neoadjuvant therapy according to the grading system we devised are significant histological outcome predictor for invasive ductal carcinoma (IDC) patients who received neoadjuvant therapy. The subjects of this study were the 318 consecutive IDC patients who had received neoadjuvant therapy in our institution. The lymph vessel tumor embolus grades in the biopsy specimens and in the surgical specimens were significantly associated with the increases in mean number of nodal metastases. Multivariate analyses with well-known prognostic factors and p53 expression in tumor-stromal fibroblasts clearly showed that the lymph vessel tumor embolus grade based on the biopsy specimens and based on the surgical specimens significantly increased the hazard rates for tumor recurrence and tumor-related death in all the IDC patients as a whole, in the IDC patients who did not have nodal metastasis, and in the IDC patients who had nodal metastasis, and the outcome-predictive power of the lymph vessel tumor embolus grades based on the surgical specimens was superior to that of the lymph vessel tumor embolus grades based on the biopsy specimens. The grades in the grading system for lymph vessel tumor emboli were significantly associated with nodal metastasis, and the histological grading system is an excellent system for accurately predicting the outcome of patients with IDC of the breast who have received neoadjuvant therapy.