Clinical benefits of tomosynthesis-guided vacuum assisted breast biopsy: a comparison with stereotactic vacuum assisted biopsy.

BACKGROUND: Tomosynthesis-guided vacuum assisted breast biopsy (3D-VAB) has been used increasingly. The aim of our study is to compare the clinical effectiveness of 3D-VAB and stereotactic vacuum assisted biopsy (2D-VAB) on the number of tissue cores containing targeted calcifications and on the procedure time. METHODS: Consecutive 87 women who underwent biopsy at our hospital from April 2020 to March 2022 for calcifications mammographically suspicious of malignancy were included in this study: 57 patients with 3D-VAB and 30 patients with 2D-VAB. RESULTS: Grouped or clustered calcified lesions were found in 39 and 21 patients among the 3D-VAB group and the 2D-VAB group, respectively. The mean number of tissue cores per biopsy containing targeted calcifications from the grouped or clustered calcified lesions was 3 and 2.3 specimens for the 3D-VAB group and for the 2D-VAB group, respectively. The mean procedure time for grouped or clustered calcifications was significantly shorter in the 3D-VAB group than in the 2D-VAB group (16.5 min vs. 27.4 min, P < 0.01). Comparing the procedure time between 3D-VAB and 2D-VAB based on calcification category, 3D-VAB had significantly shorter procedure time than 2D-VAB for both category 3 and category 4 calcification. For all patients, the mean procedure time was 18.1 min for the 3D-VAB group and 27.7 min for the 2D-VAB, thus being significantly shorter with 3D-VAB than 2D-VAB (P < 0.01). CONCLUSION: Our study demonstrated that the clinical effectiveness of 3D-VAB is superior to that of 2D-VAB and that the significant reduction in examination time with 3D-VAB is expected to benefit patients.

Erratum to immediate breast volume replacement using a free dermal fat graft after breast cancer surgery: multi-institutional joint research of short-term outcomes in 262 Japanese patients.

[This corrects the article on p. 179 in vol. 4, PMID: 26005649.].

Immediate breast volume replacement using a free dermal fat graft after breast cancer surgery: multi-institutional joint research of short-term outcomes in 262 Japanese patients.

BACKGROUND: Immediate volume replacement using a free dermal fat graft (FDFG) has been proven safe with early postoperative benefits. The aims of the present study were to clarify adequate indications and risk factors associated with operative morbidity. PATIENTS AND METHODS: A multi-institutional analysis of partial mastectomy with immediate volume replacement with FDFG was undertaken in 14 hospitals specializing in breast cancer treatment. Clinical and oncological variables were analyzed to identify factors associated with postoperative complications. RESULTS: A total of 262 cases were analyzed. Considering the observation period and overlap of patients, 13 (5.4%) out of 242 patients had complications within 1 month of surgery while 7 (4.6%) out of 151 patients developed complications 1-12 months after surgery. Two hundred and eleven out of 242 patients were statistically examined using a multivariate analysis, which revealed that the weight of resected breast tissue, size of implanted FDFG (cranio-caudal length), and weight of implanted FDFG were associated with a higher likelihood of postoperative complications. CONCLUSIONS: Immediate breast volume replacement using a FDFG after breast cancer surgery should be done for selected patients with breast cancer to avoid postoperative complications. The prospective and larger investigations are warranted for the establishment of appropriate guidelines.

Management of granulomatous mastitis: a series of 13 patients who were evaluated for treatment without corticosteroids.

Granulomatous mastitis (GM) is a rare chronic inflammatory breast condition with unknown etiology. There is still no generally accepted optimal treatment for GM. Corticosteroid treatment and/or wide excision is most commonly reported in the literature. Incision and drainage or limited excision alone has little benefit because of a strong tendency of recurrence. Corticosteroids also have a high failure rate and possible side effects. In the current series, we treated GM patients without corticosteroids, except for one patient. We also devised multidirectional deep drainage for advanced and complicated abscesses, which are characteristic of GM. This retrospective study included 13 women who met the required histologic criteria of GM. The mean age of the patients was 41 years. All of the patients were premenopausal. Six patients had breast-fed in the last 5 years. Five patients were under medication with antidepressants. A total of 11 patients developed abscesses during the clinical course, and the abscesses penetrated the retromammary space in 4 patients. We treated 2 of these 4 patients with multidirectional deep drainage and obtained complete remission in 5 and 6.5 months, respectively. These times were much shorter than those in the other 2 patients. The time to resolution in 11 patients was 4 to 28 months. This overall outcome was comparable with that of corticosteroid treatment reported in the literature. Because the natural history of GM is thought to be self-limiting, close observation and minimally required drainage of abscesses without corticosteroid administration remain the treatment modality of choice.

O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for basal-like breast cancer treated with cyclophosphamide-based chemotherapy.

The O6-methylguanine-DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O6-position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor-2+/estrogen receptor- (HER2+/ER-) and 48 (8%) basal-like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2+/ER- and 46% of basal-like subtypes were positive. The overall survival (OS) and disease-free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2+/ER- subtypes, and patients with MGMT-negative basal-like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2+/ER- and basal-like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2+/ER- subtypes treated with CPM were not significantly correlated, the patients with MGMT-negative basal-like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM-treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and predictive marker for CPM-containing chemotherapy in basal-like breast cancer.

Pathologic complete response after neoadjuvant chemotherapy in HER2-overexpressing breast cancer according to hormonal receptor status.

OBJECTIVE: For patients with HER2-positive breast cancer, the prognostic impact of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is unclear when stratified by hormonal receptor (HR) status; however, the impact of pCR on survival when stratified by hormonal receptor (HR) status is uncertain. PATIENTS AND METHODS: This multicenter retrospective study investigated the predictors of pCR and its prognostic value in Japanese patients 366 HER2-positive breast cancer who received NAC. pCR was defined as no invasive residual tumor in the breast or axilla. RESULTS: Median follow-up was 55 months. Multivariate analysis revealed that HR status (OR, 0.37; p < 0.001) was one of the independent predictors of pCR. Five-year recurrence-free survival was higher in HR-negative patients with pCR (93%) than in those without pCR (68%), and pCR was independently prognostic (hazard ratio, 0.32; p = 0.005). However, 5-year recurrence-free survival was not different between HR-positive patients with pCR (94%) and those without pCR (84%), and pCR was not significantly prognostic (hazard ratio, 0.53; p = 0.39). In addition, 5-year overall survivals were high and similar (97% in pCR, 94% in non-pCR). Among 204 patients treated with neoadjuvant trastuzumab, pCR was not significantly prognostic in the HR-positive group (hazard ratio, 0.63; p = 0.56). CONCLUSION: Our study suggested that the HER2-positive HR-positive patients had a good prognosis despite the lower achievement rate of pCR, whose prognostic impact was smaller than that in the HER2-positive HR-negative patients. The treatment strategy for HER2-positive breast cancer can be stratified by HR status.

[Four cases of double bypass surgery involving choledochojejunostomy and gastrojejunostomy for inoperable peripancreatic head cancer].

Peripancreatic head cancer often causes obstructive jaundice and duodenal obstruction, which reduces the quality of life and hinders the administration of anti-cancer drugs. Here, we report 4 cases of double bypass surgery( biliary and gastric) for the treatment of inoperable peripancreatic head cancer. The patients' ages ranged from 64 to 72 years. Two patients had pancreatic head cancer and 2 had ampullary cancer. No postoperative morbidity was observed and all 4 patients resumed oral intake within 5 days after surgery and began receiving chemotherapy within 1 month after surgery. There was immediate relief of biliary obstruction in all 3 patients with obstructive jaundice. None of the patients experienced recurrence of obstructive jaundice requiring biliary drainage. Two patients who died of cancer were able to consume food orally just before they died. Although bypass surgery is more invasive than endoscopic stenting, it may be safe and useful not only for palliation, but also for induction or continuation of chemotherapy.

[Palliative surgery for malignant bowel obstruction in patients with advanced and recurrent gastroenterological cancer].

We report the outcomes of palliative surgery for the treatment of malignant bowel obstruction in patients with advanced gastroenterological cancer. We studied 20 patients who had undergone palliative surgery over 3 years. We analyzed the clinical findings, surgical procedure, postoperative clinical course, and prognosis. The origin of the patients was colorectal cancer( 9 cases), gastric cancer( 4 cases), uterine cancer( 3 cases), pancreatic cancer( 2 cases), bladder( 1 case), and anal cancer (1 case). Small bowel obstruction was noted in 8 cases and colorectal obstruction was noted in 14 cases. Colostomy was performed in 13 cases, resection and reconstruction were performed in 6 cases, and bypass was performed in 4 cases. Ninety percent of the patients were able to eat solid food following the surgery, but 20% of the patients were forced to have bowel obstruction. The median survival time after palliative surgery was 3 (range, 0-15) months, and 6 patients (30%) died within 2 months. We concluded that palliative surgery for the treatment of malignant bowel obstruction could improve the patients' quality of life. The decision for performing palliative surgery should be made while considering the patient's prognosis, wishes, and potential for symptom improvement.

Transient effectiveness of an oral 5-Fluorouracil derivative, s-1, for epirubicin, cyclophosphamide and Paclitaxel refractory skin metastases from possible occult breast cancer in a male.

Recent chemotherapies for skin metastases from breast cancer have shown to be effective for regression, disappearance, and favorable quality of life. We describe the case of a 76-year-old male showing transient effectiveness with an oral 5-fluorouracil derivative, S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate), for epirubicin, cyclophosphamide and paclitaxel refractory skin metastases from possible occult breast cancer. The male patient was initially diagnosed as having lymph node metastases in the left axilla as possible occult breast cancer. The skin metastases developed after chemotherapy with a combination of epirubicin and cyclophosphamide, subsequent chemotherapy with paclitaxel, and radiotherapy. Chemotherapy with paclitaxel was resumed for skin metastases, but it was not effective. Alternative chemotherapy with the oral agent S-1 was administered. The skin metastases completely disappeared after the second course, but recurred at the end of the third course. This case suggests that S-1 may be a candidate for chemotherapy for skin metastases from occult breast cancer in males.

Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure.

Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC(50) of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

Relationship between thymidylate synthase (TYMS) gene polymorphism and TYMS protein levels in patients with high-risk breast cancer.

The thymidylate synthase gene (TYMS) has three functional polymorphisms which are associated with TYMS expression. To explore the predictability of TYMS polymorphisms for the sensitivity and toxicity of 5-fluorouracil (5-FU) in breast cancer patients, this study investigated the association between TYMS polymorphisms and TYMS protein expression in normal and tumour tissue specimens from 49 lymph node-positive breast cancer patients. An analysis of the TYMS 3'-UTR polymorphism showed that level of TYMS protein in normal tissue with the +6 bp/+6 bp genotype was significantly higher than that for the -6 bp/+6 bp genotype. Tumour tissue with the +6 bp/+6 bp genotype had a significantly higher TYMS protein expression than did those with other genotypes. These findings suggest that breast cancer patients with the TYMS 3'-UTR +6 bp/+6 bp polymorphism whose tumours show a 6 bp deletion within TYMS 3'-UTR represent a group that may derive the most benefit from 5-FU chemotherapy.

Hematoma-directed and ultrasound-guided breast-conserving surgery for nonpalpable breast cancer after Mammotome biopsy.

Stereotactic vacuum-assisted (Mammotome) breast biopsy is a powerful diagnostic tool for detecting microcalcifications on mammography, but it is difficult to remove the targeted lesion precisely when subsequent breast-conserving surgery is to be carried out. We achieved satisfactory results by performing hematoma-directed breast-conserving surgery after stereotactic Mammotome biopsy in seven patients. To identify the exact location of the Mammotome biopsy during the breast-conserving surgery, we created an iatrogenic hematoma in the biopsy cavity using patient's blood. This hematoma was detected easily on intraoperative ultrasonography in all patients, and was palpable as a soft mass in five of the seven patients. The microcalcifications were completely removed in all patients, and no cancer cells were found in the margin surfaces after breast-conserving surgery. There were no complications during the injection of the patient's blood into the biopsy cavity or during the hematoma-directed surgery. We describe this new procedure of hematoma-directed breast-conserving surgery following Mammotome biopsy for nonpalpable cancer with microcalcifications.

Capecitabine and paclitaxel combination chemotherapy for inoperable or recurrent breast cancer: a phase I dose-finding study by the Kinki Breast Cancer Study Group.

BACKGROUND: The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. Three-weekly XP regimens have demonstrated excellent efficacy in phase II and III trials in metastatic breast cancer. We conducted a dose-finding study to identify the recommended 4-weekly XP regimen in patients with inoperable or recurrent breast cancer for phase II evaluation. METHODS: Eligible patients had inoperable or recurrent breast cancer previously treated with chemotherapy (but not capecitabine or paclitaxel) in the (neo)adjuvant or metastatic setting. Each 4-week treatment cycle consisted of escalating doses of capecitabine (628 or 829 mg/m(2) twice daily [b.i.d.] on days 1-21) and paclitaxel (80 or 90 mg/m(2) on days 1, 8, and 15). Dose-limiting toxicities (DLT) were evaluated during the first two cycles. RESULTS: Nine patients were treated. At dose level 1 (capecitabine 628 mg/m(2) b.i.d. plus paclitaxel 80 mg/m(2)), one patient experienced a DLT (grade 3 non-hematologic toxicity). There were no further DLTs at dose level 1 or 2. Although the MTD was not reached, dose level 2 (capecitabine 829 mg/m(2) b.i.d., days 1-21, plus paclitaxel 80 mg/m(2), days 1, 8, and 15, every 28 days) is recommended for phase II evaluation, taking into consideration the single-agent doses used in Japan and the doses identified in Western studies of 3-weekly XP. The overall response rate was 44%; all patients treated at dose level 2 achieved a partial response. CONCLUSIONS: This 4-weekly XP regimen was well tolerated, active in patients with pretreated advanced breast cancer, and could be given as outpatient treatment. These results are consistent with findings of phase II and III trials evaluating 3-weekly regimens, and indicate that further investigation of a 4-weekly XP regimen is warranted.

Quantitative analysis of the reconstructed breast using a 3-dimensional laser light scanner.

Postoperative cosmesis of the reconstructed breast depends on the interrelation of shape, size (volume), and symmetry. In this study, reconstructed breasts were analyzed with 3-dimensional projections generated by laser light scanning. Fifty-one cases of breast reconstruction following mastectomy (16 cases of rectus abdominis flap, 15 cases of latissimus dorsi flap, and 20 cases of tissue expansion) were evaluated 6 months postoperatively. Shape, volume, and symmetry were quantitatively evaluated. Captured images of the normal breast were mirror-reversed and superimposed on images of the reconstructed breast. Differences in the generated Moire patterns were used to quantitatively compare breasts. The method was rapid, reproducible, and accurate in comparison to thermoplaster casts. It was found that rectus abdominis flaps applied following total mastectomy and latissimus dorsi flaps applied following partial mastectomy gave the best results for their relatively low degree of asymmetry. Application of tissue expansion led to greater asymmetry and poorer overall cosmesis. In conclusion, a 3-dimensional laser light scanning system makes it possible to quantitate the cosmetic outcome following breast reconstruction.

Clinical experience of weekly paclitaxel-based treatment as preoperative chemotherapy for patients with primary breast cancer.

BACKGROUND: Paclitaxel is an effective agent in the treatment of metastatic breast cancer. The aim of this study was to evaluate the safety and efficacy of weekly paclitaxel-based preoperative chemotherapy in patients with large operable breast cancer. METHODS: Patients initially received paclitaxel as a 3-hour infusion at 175 mg/m2. Three weeks after initial administration, two cycles of three weeks of paclitaxel 80 mg/m2 over a 1 hour infusion followed by a one week break were given. Of 22 patients, 9 had stage II (tumor diameter greater than 3 cm), 4 stage III A, 7 stage III B, and 2 stage IV (with ipsilateral supraclavicular lymph node metastasis) cancer, respectively. RESULTS: Excluding stage IV patients, the overall response rate to paclitaxel chemotherapy was 80%. Four of the 20 patients (20%) showed a clinical complete response (cCR). Two of these showed pathologic complete response and the other 2 had only the ductal component remaining. The primary tumor response and axillary lymph node downstaging following preoperative chemotherapy tended to be related in 16 patients with clinically positive nodes. Breast conserving surgery was performed as a result of downstaging in the 9 stage II patients. Grade 3 neutropenia occurred in one patient when 175 mg/m2 of paclitaxel was administered, but no serious side effects developed during the weekly administration of paclitaxel. CONCLUSION: The use of weekly paclitaxel-based preoperative chemotherapy appears to yield a significant anti-tumor effect without inducing serious drug-related adverse effects. Furthermore, the effectiveness of this treatment appears to result in a higher frequency of breast conserving surgery.

Dynamic multidetector CT of breast tumors: diagnostic features and comparison with conventional techniques.

OBJECTIVE: We sought to analyze the features of breast tumors as revealed on dynamic multidetector CT (MDCT), to develop descriptors for these features, and to compare the performance of MDCT with the performance of other techniques used in the depiction of tumors. SUBJECTS AND METHODS. MDCT was performed in 149 women with suspected breast tumors, and 173 breast lesions were detected. These breast lesions were classified as either mass or nonmass enhancing lesions. For mass lesions, the margin, shape, and enhancement patterns were evaluated. For nonmass enhancing lesions, the distribution of enhancement and the types of time-density curve patterns were evaluated. MDCT was compared with mammography and sonography as a method of revealing breast tumors. RESULTS: Of the 173 breast lesions detected, 150 were mass lesions, 131 (87%) of which were malignant. Of the 23 nonmass enhancing lesions, 21 (91%) were malignant. The most highly predictive features for lesion malignancy were an irregular margin (100%), an irregular shape (99%), and rim enhancement (100%). Similar features were the most accurate signs of malignancy--a spiculated and irregular margin (90%). On time-density curves, the washout and plateau patterns showed high positive predictive value (93%) and sensitivity (91%) for malignancy. However, these patterns had low negative predictive value (42%) and specificity (48%). Seven breast lesions that could not be detected on mammography or sonography were identified on MDCT. MDCT more accurately revealed the margin of the tumor invasion in 11 breast tumors than did mammography or sonography. CONCLUSION: The features revealed on MDCT can help to distinguish benign lesions from carcinomas. MDCT can add to the data obtained with mammography or sonography in patients with suspected breast tumors.