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Purpose: Partial-breast irradiation (PBI) has been performed as alternative to whole-breast irradiation (WBI) in breast-conserving therapy (BCT). Recently, the 21-gene recurrence score (RS) was introduced to determine the adjuvant therapy for estrogen receptor (ER)-positive, and human epidermal growth factor receptor 2 (HER2)-negative diseases. However, the impact of RS-based systemic therapy on locoregional recurrence (LRR) following BCT with PBI remains uninvestigated., Methods and Materials: Patients with ER-positive, HER2-negative, and node-negative breast cancer who underwent BCT with PBI were examined during May 2012-March 2022. In addition to immunohistochemistry (IHC), RS was available to decide on adjuvant therapy., Results: In total, 431 patients were evaluated with a median followup of 48.6 months. The 4-year LRR-free survival rates were 97.3% and 96.4% in the IHC and RS cohorts, respectively (p = 0.50). Ki67 of >20% was significantly associated with LRR in the multivariate analysis (HR 4.39, p < 0.05). For patients with Ki67 > 20%, 29 of 71 (40.8%) and 46 of 59 (78.0%) patients received only endocrine therapy in the IHC and RS cohorts, respectively (p < 0.0001). For patients with Ki67 >20% who received only endocrine therapy, the 4-year LRR-free survival rates were 91.8% in the IHC cohort and 94.6% in the RS cohort (p = 0.29) CONCLUSIONS: Although the introduction of RS increased the number of patients receiving endocrine therapy alone for Ki67 >20% of disease by two times, the LRR-free survival after BCT with PBI could be maintained. However, further studies from multiple institutions with longer followup data are required., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Partial-breast irradiation (PBI) needs accurate cavity delineation with computed tomography (CT). In perioperative PBI using multicatheter-interstitial brachytherapy (MIB), catheters implanted during surgery were enabled as fiducial markers. Magnetic resonance imaging (MRI) can also assist delineation with CT., Methods: Patients receiving MIB-PBI were analyzed. Cavity visualization scores (CVSs) were categorized with CT. With catheter-based delineation (CBD), the relationship between cavity boundaries and catheters were used to contour the tumor bed. Co-registered MRI delineation (CMD) was also performed. The correlation between cavity volume and the excised tissue weight was compared for the two techniques., Results: The association between CVS and preoperative characteristics in 159 patients showed mammographic breast density (MBD) remained correlated to CVS on multiple regression analyses; CVS = 5.2-0.61 x MBD (p < 0.0001). In 43 patients, the cavity volumes determined with CBD vs CMD were 12.8 ± 6.4 cm 3 vs 16.1 ± 12.4 cm 3 (p < 0.0001), and their plots with excised weights showed the best fitting lines were 0.29 vs 0.48 (p < 0.0001), respectively. The correlation coefficients for CBD vs CMD were 0.65 vs 0.55 (p = 0.20) in low (CVS 1-3, n = 27) and 0.72 vs 0.58 (p = 0.36) in high visualized cavities (CVS 4-5, n = 16), respectively., Conclusions: The use of implanted catheters as fiducial markers was associated with smaller cavities and greater correlations with the excised tissue weights than co-registration with MRI. This might be a useful technique, especially for patients with dense breasts on mammography., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The role of astrocytes in the periphery of metastatic brain tumors is unclear. Since astrocytes regulate central nervous metabolism, we hypothesized that changes in astrocytes induced by contact with cancer cells would appear in the metabolome of both cells and contribute to malignant transformation. Coculture of astrocytes with breast cancer cell supernatants altered glutamate (Glu)-centered arginine-proline metabolism. Similarly, the metabolome of cancer cells was also altered by astrocyte culture supernatants, and the changes were further amplified in astrocytes exposed to Glu. Inhibition of Glu uptake in astrocytes reduces the variability in cancer cells. Principal component analysis of the cancer cells revealed that all these changes were in the first principal component (PC1) axis, where the responsible metabolites were involved in the metabolism of the arginine-proline, pyrimidine, and pentose phosphate pathways. The contribution of these changes to the tumor microenvironment needs to be further pursued.

Purpose: Multicatheter interstitial brachytherapy (MIB) and external-beam (EB) radiotherapy are established partial-breast irradiation (PBI) techniques. Although EB-PBI is widely available, it requires extra irradiated margins for target uncertainties. We examined the impact of EB-PBI on dose-volume constraints as compared to MIB-PBI., Methods and Materials: Among 653 patients receiving MIB-PBI between October 2008 and April 2020, consequent 159 patients after September 2018 were examined. Clinical target volume (CTV) included the lumpectomy cavity plus 1.0 cm. Planning target volume (PTV) for EB-PBI was defined as CTV with 1.0-cm expansion. Because the ratio of PTV to breast volume (RPB) was related to cosmesis, <25% of RPB was defined as suitable for the ipsilateral breast constraints. Preoperative breast size was classified as very small (<350 cm 3 ), small (350-699 cm 3 ), and medium or large (≥700 cm 3 ). According to each category, the dose-volume constraints of the organs at risk were compared between the two PBI techniques., Results: Patients including 84 very small, 59 small, and 16 moderate to large breasts were examined. Although RPB was suitable in all patients receiving MIB-PBI, it was achieved in 74 patients (46.5%) receiving EB-PBI (p < 0.0001). The suitable RPB in patients with very small, small, and moderate to large breast was 32.1%, 55.9%, and 100%, respectively (p < 0.0001). Normal-tissue constraints for the other organs could be satisfied in patients with moderate to large breasts., Conclusion: Although EB-PBI may be an appropriate option for patients with moderate to large breasts, MIB-PBI could still be a crucial technique, especially for patients with small breasts., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Brachytherapy-based partial-breast irradiation (PBI) is a treatment option for breast-conserving therapy. Although intraoperative catheter implantation has been introduced, early wound complications are a concern. Covert operations with a moving incision are widely performed to hide surgical scars and may reduce the incision-site radiation dose. This study aimed to compare complication rates for moving incision and conventional incision in covert breast-conserving surgery., Methods and Materials: Between October 2008 and December 2018, the medical records of all patients who underwent PBI using multicatheter interstitial brachytherapy after breast-conserving surgery were examined. Since July 2016, to hide the scar, we have performed a moving incision from above the tumor to an invisible site at our institution. The planning target volume included 1.0-1.5 cm of tissue surrounding the surgical cavity. High-dose-rate interstitial brachytherapy with a dose of 32 Gy in eight fractions was performed. The cumulative incidences of surgical site infections and symptomatic seromas ≤90 days were analyzed., Results: The study included 516 consecutive patients with 526 lesions. Overall, 40 (7.6%) early wound complications were observed, in which 4 (2.6%) involved 152 moving incisions and 36 (9.6%) involved 374 conventional incisions (p = 0.01). On univariate analysis, age, tumor diameter, re-excision, planning target volume, numbers of catheters and planes, and incision type were risk factors for complications. On multivariate analysis, only incision type was a risk factor. Moving incision reduced the early complication rate by 75% (p = 0.01)., Conclusion: Moving incision in covert breast-conserving surgery reduced the risk of early wound complications., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Based on the accumulating evidence for equivalent results of partial-breast irradiation (PBI) and whole-breast irradiation (WBI) in breast-conserving therapy (BCT), the American Society for Radiation Oncology (ASTRO) updated the consensus statement (CS) to expand the range of potential candidates for PBI outside clinical trials. Of the various techniques, PBI using multicatheter interstitial brachytherapy (MCB) is the oldest and has long-term data. In this study, the efficacy of single-stage BCT using MCB-PBI achieved by an intraoperative catheter placement was validated on updated ASTRO guidelines. We retrospectively examined patients undergoing BCT using MCB-PBI or WBI. The updated CS distinguished patients aged 40-49 years with ER+, tumor ≤2 cm, and margin ≥2 mm from unsuitable patients in the previous CS. We compared the ipsilateral breast tumor recurrence (IBTR) rate in MCB-PBI with that in WBI patients with suitable or cautionary (S/C) categories on the updated CS. Between November 2007 and September 2017, 641 patients with 647 lesions underwent BCT (MCB-PBI, 407; WBI, 240). At the median follow-up time of 54.4 months, we observed 8 (1.97%; 95% CI: 0.62-3.31%) and 7 (2.92%; 95% CI: 0.79-5.05%) IBTRs, respectively. Updating the CS increased the S/C patients receiving MCB-PBI from 232 patients (57.0%) to 319 (78.4%). Comparison of clinical outcomes at the 12-month minimum follow-up between 291 MCB-PBI and 103 WBI in S/C patients showed no significant differences in the 4-year rate of IBTR-free (100% vs 98.9%; P = 0.29) and disease-free survival (98.7% vs 95.5%; P = 0.24). Overall, single-stage BCT using MCB-PBI offered similar tumor control rates, compared with WBI, on the updated ASTRO CS.

Background: Partial breast irradiation (PBI) is an alternative to whole breast irradiation (WBI) for breast-conserving therapy (BCT). A randomised phase 3 trial demonstrated that PBI using multicatheter brachytherapy had an equivalent rate of local recurrence, disease-free survival, and overall survival as compared to WBI. However, limited data are available on PBI efficacy for young patients with breast cancer., Methods: We evaluated consecutive patients with Tis-2 (≤ 3 cm) N0-1 breast cancer who underwent BCT. For PBI, patients received radiotherapy using multicatheter brachytherapy in an accelerated manner with a dose of 32 Gy in eight fractions over 5-6 days. For WBI, patients received an external beam radiation therapy that was applied to the entire breast with a total dose of 50 Gy in fractions of 2 Gy for 5 weeks. Two hundred seventy-four patients with 278 lesions received PBI; 190 patients with 193 lesions received WBI., Results: Patients aged <50 years including 98 women with 99 lesions receiving PBI and 85 women with 85 lesions receiving WBI were selected. Ipsilateral breast tumor recurrence rate was 3.0 and 2.4 % by PBI and WBI, respectively (P = 0.99). There was no significant difference in 4-year probability of disease-free survival (97.6 and 91.4 % for PBI and WBI, respectively; P = 0.87)., Conclusions: This is the first report of PBI efficacy in young patients in Asia. Although it is a nonrandomized retrospective chart review of a small cohort of patients with a relatively short follow-up period, PBI may be a better option than WBI following BCS in some young patients with breast cancer.

Breast cancer confined within the lactiferous duct or lobule, without invading the stroma, is called ductal carcinoma in situ (DCIS), whereas breast cancer that has invaded the stroma through the basal membrane is called invasive cancer. Heparanase, an endo-beta-D-glucuronidase that specifically degrades heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM), plays an important role when breast cancer cells breach the basal membrane. Recently, we have reported that heparanase is involved in angiogenesis through direct induction of cyclo-oxygenase-2 (COX-2). COX-2 induces vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and is thus involved in neovascularization. The present study was undertaken to analyze surgically resected breast cancer specimens for heparanase and COX-2 expression, using specimens from 59 patients with invasive cancer and 85 patients with DCIS (including 41 cases of DCIS adjacent to invasive cancer). This study yielded the following results: a) the distribution of heparanase within tumor tissue was identical to that of COX-2; b) heparanase expression was more frequent in invasive cancer than in non-invasive cancer; c) a close positive correlation was noted between heparanase and COX-2 expression (this correlation was particularly strong in cases of invasive cancer); and d) COX-2 expression was always seen in cases positive for heparanase expression. Our results indicate that heparanase expression increases during the progression of breast cancer into invasive cancer, and that this change is accompanied by increased COX-2 expression. They also suggest that heparanase may play a novel role for COX-2 mediated tumor angiogenesis in breast-cancer progression.

A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6-49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6-100) days to onset of and median duration of response was 125 (36-305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1-3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1-3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.

In patients with breast cancer who had undergone breast conservative treatment involving lumpectomy, axillary lymph node dissection and irradiation, the surgical results and risk factors for remaining cancer foci in the conserved breast were investigated. This form of surgery was performed in 25 patients with T1,N0,-Ia,M0 breast cancer. The cut end of the resected specimen was histopathologically positive for cancer cells in 48% of the patients, but there has been no local or distant recurrence in any patient to date with a mean follow-up period of 17.2 months after surgery. In most breasts resected after lumpectomy, slight cancer foci remained in mammary glands at the sites within 1.0cm distant from the cut end. Extensive remaining cancer lesions were found among cases with advanced intraductal spread or central necrosis in the intraductal foci. The above findings indicate that breast conservative treatment by lumpectomy may result in histopathologically remaining cancer foci, although these can be controlled by irradiation therapy. However, application for this treatment requires much caution when severe intraductal spread or central necrosis is present in the intraductal foci, because extensive cancer foci may remain postoperatively in such cases.

Radiation dose-effect relationship is reviewed. In conservative treatment of early breast cancer, necessity of radiation is discussed and surgery with radiotherapy technique in our hospital is presented. Our procedures consist of lumpectomy which is removal of 1 cm of normal tissue containing primary breast cancer and complete axillary dissection and postoperative radiotherapy of 46 Gy with 9 Gy of electron boost. Since November 1987, 51 patients treated by this procedure have shown a good local control and a satisfactory cosmetic results. We can conclude that the positive aspects of radiotherapy in the management of conservative therapy for early breast cancer are overwhelming.

We have investigated the usefulness of combination therapy with radiation and HCFU for advanced and recurrent breast cancer according to a clinical controlled multicenter trial from 1982 to 1984. One hundred cases were registered and 82 of them were available. Treatment sites were the lymph nodes, skin, bone and lung, and the overall response rate was 58% in CR and 19% in PR, while the duration of remission was 18 weeks in CR. Side effects were found in 10% of the patients. Combination therapy with radiation and HCFU may be useful in multimodal treatment for advanced recurrent breast cancer.

Treatment of operable breast carcinoma by radical irradiation instead of total mastectomy was discussed in conformity with our experiences and reports. No significant differences were obtained between conservative management and radical mastectomy in the rate of locoregional control and survival. The cosmetic results were satisfactory in almost all of patients. This method must be considered and established on concepts based on the multimodal treatment of breast carcinoma in Japan.

Sixty-nine patients have shown recurrence after curative (standard, extended and modified) mastectomy from 1969 to 1978 in our department. Recurrence patterns and prognostic factors were analyzed using life-table and log-rank methods. Thirty-four patients (49%) developed their first recurrence within two years after surgery and died within two years after that. This period seemed to be high-risk after surgery and first recurrence. The disease-free interval and survival after first recurrence seemed to be shorter with the more advanced presenting Tnm stage. The disease-free and recurrence-to-death intervals of patients with first loco-regional recurrence seemed to be longer than those with first distant metastases.

The subjects were 15 patients with primary mammary cancer who underwent radical mastectomy. Axillary dissection (level I, II and III) with an incision 7 cm below the axilla was performed. After radical mastectomy, the presence/absence of remaining lymph nodes and fatty tissue was determined. All operations were performed by the same surgeon. The number of lymph nodes dissected by means of subaxillary incision ranged from 10 to 32 (mean 20.4). The proportion of remaining lymph nodes found after radical mastectomy was 0/142 (0%) for level I, 0/113 (0%) for level II and 3/54 (5.6%) for level III. In the subclavian Halsted area, fatty tissue partially remained in 60.0% of the patients and more than half in 13.3%. It was shown that complete dissection of level III lymph nodes is difficult when this surgical technique is employed. Although fatty tissue did remain in some cases after level II dissecting, this technique presented hardly any problems in the case of level I and II dissection. Therefore, from the viewpoint of axillary dissection alone, the present technique can achieve results similar to those obtained by radical mastectomy, suggesting its applicability to mammary cancer at a relatively early stage.