Infiltration of CD4, CD8, CD56, and Fox-P3-positive lymphocytes in breast carcinoma tissue after neoadjuvant chemotherapy with or without trastuzumab.

BACKGROUND: Trastuzumab (Tz) is assumed to prime antibody-dependent cellular cytotoxicity (ADCC); however, it remains unclear whether Tz therapy can clinically induce adaptive cellular immunity. OBJECTIVE: Adaptive Cellular Immune Effect of Tz Therapy. METHODS: This study included 29 surgical invasive breast carcinomas administered neoadjuvant chemotherapy with Tz (15 cases) or without Tz (14 cases). The numbers of immunoreactive cells (CD4, CD8, CD56, and Fox-P3) in three different compartments (intratumoral, adjacent stromal, and distant stromal) were determined. RESULTS: The average number of adjacent stromal CD4-positive, CD8-positive, and Fox-P3-positive cells in the Tz+ group was significantly greater than that in the Tz- group (p = 0.036, 0.0049, and 0.043, respectively). However, the number of Fox-P3-positive cells was much less than that of CD4-positive cells. Moreover, distant stromal CD4-positive and CD8-positive cells in the Tz+ group was also significantly greater than that of the Tz- group (p = 0.029 and 0.032, respectively). Only a small number of CD56-positive natural killer cells, playing a main role in ADCC, accumulated at the tumor site after Tz therapy. CONCLUSIONS: The results suggest that Tz therapy induces adaptive cellular immunity, including infiltration of both CD4-positive helper T cells and CD8-positive cytotoxic T cells into the breast carcinoma lesion.

Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling.

BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors. METHODS: We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering. RESULTS: The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters. CONCLUSION: Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk.

[Two Cases of Unresectable/Advanced Breast Cancer with Pathological Complete Response after Combination Chemotherapy with Pertuzumab. Trastuzumab, and Docetaxel].

Combination chemotherapy with pertuzumab, trastuzumab, and docetaxel is recommended as the first-line treatment for patients with HER2-positive unresectable or metastatic breast cancer. We report 2 cases of unresectable breast cancer for which pertuzumab, trastuzumab, and docetaxel therapy was effective. Case 1: A woman in her 40s was diagnosed with TxN3aM0, Stage ⅢC, HER2-positive, hormone receptor-positive advanced breast cancer. After administration of 6 courses of pertuzumab, trastuzumab, and docetaxel therapy, she underwent surgery(Bt+Ax[Ⅱ]). Histopathological examination revealed that chemotherapy effect was Grade 3. Case 2: A woman in her 60s was diagnosed with de novo Stage Ⅳ, HER2- positive, hormone receptor-negative breast cancer. She was administered 8 courses of pertuzumab, trastuzumab, and docetaxel therapy as the third-line treatment, because she initially refused treatment. Thereafter, she underwent surgery(Bt+Ax [Ⅰ]). In both cases, histopathological examination revealed complete response after chemotherapy. Thus, combination therapy of pertuzumab and trastuzumab may improve the prognosis in patients with HER2-positive breast cancer.

Predictive detection areas for identifying additional MRI-detected breast lesions on second-look ultrasonography.

PURPOSE: Identifying an additional MRI-detected breast lesion on second-look ultrasonography (US) is technically challenging because of lesion displacement with the patient's position change. The aim of this study is to help identify MRI-detected lesions on second-look US by developing a probing area, called "the predictive detection area" (PDA), and by assessing the PDA. METHODS: We measured the nipple-to-lesion distances (NLDs) for 16 breast lesions on prone- and supine-position MRI sets and calculated the difference and angle between the two NLD vectors, representing the lesion displacement. The minimum and maximum differences and angles were chosen to form the PDA. Another 22 breast lesions, detected in the prone MRI, were identified on US by probing the PDA to evaluate the probability of existence. RESULTS: The width between the minimum and maximum differences in two NLDs and the angle to form the PDA for the upper-inner, upper-outer, and lower-outer quadrants were 23.0 mm and 95.0°, 29.0 mm and 41.0°, and 18.0 mm and 17.0°, respectively. The respective probabilities of existence were 100, 80, and 100%. CONCLUSIONS: The PDA had a high probability of existence and was acceptably accurate; therefore, the PDA in a second-look US has the potential to help operators to quickly identify additional MRI-detected lesions.

Immunohistochemical analyses of CD44 variant isoforms in invasive micropapillary carcinoma of the breast: comparison with a concurrent conventional invasive carcinoma of no special type component.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a distinct histopathological variant of breast carcinoma and frequently develops lymph node metastases. CD44 is a family of transmembrane glycoprotein receptors with multiple variant isoforms (CD44v), which have tissue-specific expression. Previous studies have demonstrated a loss or gain of CD44v and CD44 standard form (CD44s) expression in breast carcinomas. In this study, we analyzed the immunoprofiles of CD44s, CD44v6, and CD44v9 in IMPC and compared them with those in a concurrent invasive carcinoma of no special type (ICNST) component, thus clarifying the significance of CD44 expression in IMPC. METHODS: Twenty-one consecutive cases of mixed IMPC were included in this study. The expression statuses of CD44s, CD44v6, and CD44v9 in both the IMPC and ICNST components were analyzed semiquantitatively by immunohistochemistry. RESULTS: The immunohistochemical scores of CD44s, CD44v6, and CD44v9 were significantly decreased in the IMPC component compared to the ICNST component (p = 0.00335 for CD44s, p = 0.000982 for CD44v6, and p = 0.00271 for CD44v9). Moreover, the immunohistochemical scores of CD44v6 in the IMPC component and CD44v9 in the ICNST component of lymph node metastasis cases were significantly lower compared to cases without lymph node metastasis (p < 0.01). CONCLUSIONS: Decreased CD44 expression may play an important role in promoting lymph node metastasis in IMPC through an inability or decreased capacity to bind with the surrounding stroma. Moreover, high CD44s+ expression levels in the concurrent ICNST component may be related to the development of IMPC.

Umbilical metastasis derived from breast cancer: report of a case.

Umbilical metastases mainly arise from malignancies of the digestive and gynecological systems, but rarely from breast cancer. A 64-year-old woman with a history of breast cancer was referred to us for investigation of a painful lesion in the umbilicus. Immunohistochemical staining of a specimen obtained by biopsy from the nodule showed umbilical metastasis of breast cancer. After a work up, she was successfully treated with a combination of surgery and endocrine therapy. We report this case to reinforce that not all periumbilical tumoral deposits are consistent.

Prognostic impact of CD10 expression in clinical outcome of invasive breast carcinoma.

BACKGROUND: Early diagnosis and treatment for breast cancers has greatly improved in recent years, however, subset of this disease with early recurrence have remained to be unpredictable. Several studies has addressed that strong CD10 expression in tumor stroma is associated with poor survival rate of breast cancers, but no correlation between CD10 expression and disease-free survival has been elucidated yet. For these reasons, this study with modified immunohistochemical (IHC) staining evaluated the expression of CD10 in invasive breast carcinomas (IBCs) and analyzed correlations between CD10 expression on tumor cells, stromal cells and myeloid-like cells with clinicopathological parameters and recurrence status. METHOD: IHC staining method was performed on formalin-fixed paraffin-embedded sections of 73 cases of primary IBCs, with record of pathological characteristics of subjects followed up from 1998 to 2007. RESULTS: Stromal CD10 expression was observed in 39/73 cases (53.4 %) with strong expression in 41.0 %. Three cases stained positive for myeloid-like cells and five for carcinomatous cells, of which 6 cases had recurrence and/or regional LN status. Stromal CD10 expression was significantly higher in the unfavorable group (69.6 %; 16/23 cases) compared with the favorable group (32.1 %; 9/28 cases) (p = 0.048). The levels of CD10 expression showed significant difference among clinical outcomes (recurrence or non-recurrence), independent of regional LN status (p = 0.034), histology type (p = 0.044), ER status (p = 0.042), PgR status (p = 0.039), Her2 status (p = 0.038) and Ki67 index (p = 0.036) (partial Pearson correlations). Cox proportional-hazards regression showed that risk factors for disease-free survival were stromal CD10 expression [CD10±, CD10+ versus CD10++; p = 0.003; HR 2.824 (1.427-5.591)]; regional LN status [N0, N1, N2, versus N3; p = 0.004; HR 2.107 (1.262-3.517)] and PgR status [negative versus positive, p = 0.006, HR 0.172 (0.049-0.596)]. CONCLUSION: CD10 expression on stroma with or without other positive tumor cells and/or myeloid-like cells may function as a powerful prognostic factor for IBC disease-free survival rates, predicting of potential recurrence. It can be determined by a simple modified IHC staining method, which is independent of other prognostic morphologic markers and biomarkers in IBC.

[Evaluation of breath alcohol concentration after the administration of alcohol-based docetaxel].

In the present study, we measured breath alcohol concentration(BAC)after the administration of alcohol-containing docetaxel(OTX)in breast cancer patients, and examined the safety of OTX outpatient administration. Twenty breast cancer patients who received OTX chemotherapy at our outpatient facility were included. The administered doses were 100mg/m2 in 5 cases, 75mg/m / 2 in 13 cases, and 60 mg/m2 in 2 cases. BAC was measured 3 times: immediately after infusion, 30 minutes after infusion, and 60 minutes after infusion. No symptoms of hot flash or drunkenness due to alcohol were observed. BAC was detected in 10 cases(50%)immediately after infusion, in 7 cases(35%)at 30 minutes after infusion, and in 1 case(5%) at 60 minutes after infusion. BAC was more than 0.15mg/L in only 1 case(5%)and reduced to less than 0.15mg/L in all cases after 30 minutes. Our results suggest that the effects of alcohol are alleviated 60 minutes after infusion and that patients receiving OTX could return home safely.

Magnetic resonance imaging shrinkage patterns following neoadjuvant chemotherapy for breast carcinomas with an emphasis on the radiopathological correlations.

Preoperative neoadjuvant chemotherapy (NAC) is considered to be the standard treatment for locally-advanced breast carcinomas. Obtaining precise information regarding the tumor extent and distribution by imaging modalities to assess the success of breast-conserving surgery following NAC is extremely important. Analysis of the detailed radiopathological correlation of magnetic resonance imaging (MRI) following NAC has not been reported previously. The MRI and histopathological shrinkage patterns of residual breast carcinomas in 27 consecutive cases were analyzed following NAC and classified into five categories: Types I and II (concentric shrinkage with and without surrounding lesions, respectively); type III (shrinkage with residual multinodular lesions); type IV (diffuse contrast enhancement in whole quadrant); and non-visualization. The present study clearly demonstrated that the most common MRI shrinkage pattern was type I (11 cases), followed by type II and non-visualization, and the most common histopathological shrinkage pattern was type II (11 cases), followed by type III (8 cases). The concordance rate between MRI and pathological patterns was 48% and the worst concordance MRI pattern was type I. MRI is considered to be a useful method for evaluation of the residual carcinoma following NAC. However, the concordance rate was low in the MRI pattern I cases and tiny foci of residual carcinoma were present in half of the non-visualization cases, as shown by MRI. Therefore, the tumor extent must be completely resected for patients who undergo NAC, and postoperative radiation may be important for preventing local recurrence of breast carcinoma.

[A case of breast cancer with repeated cardiac dysfunction due to trastuzumab].

Here we present a case of breast cancer in which cardiac dysfunction had previously been observed on trastuzumab(TRS) administration; the condition then improved but reoccurred on readministration of TRS. A 52-year-old woman received preoperative chemotherapy for StageIIIC left breast cancer(fluorouracil, epirubicin and cyclophosphamide followed by docetaxel and TRS), and then underwent partial mastectomy and axillary lymph node dissection. For adjuvant therapy, she received endocrine therapy and TRS. Radiation therapy was administered to the left residual breast. The patient complained about palpitation in the 5th cycle of TRS, and left ventricle ejection fraction(LVEF)decreased to 45.3% from 64%. Therefore, we stopped TRS administration. Palpitation improved, and LVEF increased to 53% after 2 months. TRS was administered again; however, palpitation reoccurred and LVEF decreased to 44%. TRS administration was once again discontinued. However, according to the HERA trial report regarding patients with a history of anthracycline and radiation therapy, TRS administration could be resumed when LVEF is greater than 50%, but we should be more careful during readministration of TRS.

Mucinous carcinoma occurring in the male breast.

Male breast carcinoma is an uncommon neoplasm, accounting for 0.6% of all breast carcinomas. Invasive ductal carcinoma of no special type is the most common type of male breast carcinoma, and mucinous carcinoma occurring in the male breast is extremely rare. In the present study, we report a case of mucinous carcinoma of the male breast and discuss the clinicopathological features of this type of tumor. A 63-year-old Japanese male presented with a gradually enlarged nodule in the right breast. The resected breast specimen revealed pure mucinous carcinoma and immunohistochemical analyses demonstrated that tumor cells were positive for estrogen receptor (ER), but negative for progesterone receptor (PgR). In addition, HER2 expression was not amplified. Pure mucinous carcinoma is generally associated with a low incidence of lymph node or distant metastases, and excellent disease-free survival in females. However, certain cases of this type of tumor with axillary lymph node metastasis in the male breast have been reported. In addition, the immunoprofiles of mucinous carcinoma in males are fundamentally the same as those in females. More than 90% of cases show positive immunoreactivity for ER and/or PgR, and HER2 expression is not amplified. However, it has been reported that breast cancer in males is more frequently positive for ER than in females, and has less HER2 overexpression. The high rate of hormone receptor-positive breast cancer in males is considered to be due to similar conditions as those in breast cancer in postmenopausal women. The pathogenesis of male breast carcinoma, including mucinous carcinoma, remains unclear; therefore, additional clinicopathological studies are required.

Feasibility of prior administration of cyclophosphamide in TC combination treatment.

BACKGROUND: TC (docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) q3w) combination is used for neoadjuvant/adjuvant chemotherapy in primary breast cancer. The incidence of allergic reaction is reportedly more common in patients who receive docetaxel before cyclophosphamide. This study aims to determine the significance of cyclophosphamide and docetaxel administration sequence. METHODS: Prospective analysis was performed of 49 consecutive patients treated with TC for stage I-IIB breast cancer from March 2010 to June 2011. Premedication was administered with granisetron, dexamethasone, and chlorpheniramine. Patient charts were reviewed for completion rate and adverse events. Two-tailed Fisher exact test was used to evaluate adverse events between prior cyclophosphamide and prior docetaxel. RESULTS: Of 49 patients, 26 received docetaxel prior to cyclophosphamide and 23 received cyclophosphamide before docetaxel. There were no differences in patient characteristics between the two groups. Completion rates were 95.6 % in the prior cyclophosphamide group, and 100 % in the prior docetaxel group. The relative dose intensities of docetaxel and cyclophosphamide were 94.5 and 94.8 % in the prior cyclophosphamide group, and 98.5 and 98.7 % in the prior docetaxel group (p < 0.01). In the prior cyclophosphamide group, severe neutropenia occurred in 96 % of patients, but in only 46 % of patients in the prior docetaxel group (p < 0.01). Significantly fewer cases of skin eczema (27 versus 61 %), nausea (8 versus 48 %), stomatitis (23 versus 61 %), and diarrhea (4 versus 30 %) were observed in the prior docetaxel group as compared with the prior cyclophosphamide group (p < 0.01). Decreased incidences of fatigue (50 versus 65 %) and edema (19 versus 35 %) were found in the prior docetaxel group (p < 0.05). No difference was observed in allergic reaction or neuropathy between the two groups. CONCLUSION: Patients receiving cyclophosphamide prior to docetaxel were at increased risk of several toxicities as compared with patients receiving docetaxel prior to cyclophosphamide in TC combination therapy.

Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers.

Protein-bound polysaccharide-K (PSK) enhances the antitumor effect of anticancer drug when used clinically in combination with such drugs. PSK is known to act by immune-mediated mechanisms; however, the relationship between PSK and metabolic enzymes of anticancer drugs is unknown. We used the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) clinically to evaluate the sensitivity of anticancer drugs. In the present study, we modified the CD-DST by adding peripheral blood mononuclear cells (PBMCs) (immuno-CD-DST) and examined the antitumor effect of PSK in combination with anticancer drugs. First, HCT116 human colon cancer cells were cultured with PSK and 5-fluorouracil (5-FU) or 5'-deoxy-5-fluorouridine (5'-DFUR) in the presence or absence of PBMCs, and the antiproliferative effects were compared. In the presence of PBMCs, PSK augmented the inhibitory effects of 5-FU and 5'-DFUR on HCT116 cell proliferation. Next, using human gastric cancer and colon cancer cell lines, the effects of PSK on mRNA expression of various metabolic enzymes of fluoropyrimidines: dihydropyrimidine dehydrogenase (DPD), thymidylate synthase, thymidine phosphorylase and orotate phosphoribosyl transferase, were examined by real-time PCR. PSK significantly enhanced DPD mRNA expression in all of the cancer cell lines tested, but not those of the other enzymes. Addition of IFN-α and TRAIL, cytokines known to inhibit DPD expression, to the cultures reduced DPD mRNA expression in the cancer cells. When PBMC samples collected from healthy volunteers were cultured with PSK, IFN-α mRNA expression increased in 3 of the 5 PBMC samples, while TRAIL mRNA expression was unchanged. The present results propose the possibility that PSK induces PBMCs to express IFN-α which inhibits DPD expression, and consequently augments the antitumor effect of 5-FU or 5'-DFUR. Immuno-CD-DST is useful for evaluating drugs with immunological mechanisms of action.

Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report.

In July 2008, cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), was approved in Japan for clinical use against chemotherapy-refractory metastatic colorectal cancer (mCRC). At Shiga University of Medical Science, between December 2007 and April 2012, a total of 24 EGFR-positive mCRC cases were administered immunohistochemistry with cetuximab as salvage monotherapy. The safety, side-effects and clinical efficacy of the treatment, including response rate, time to treatment failure, progression-free and overall survival, K-ras mutation status and impact on outcome, were investigated. The patient tumor growth control rate (TCR) was 38%, the mean time to progression (TTP) was 9.8 weeks [95% confidence interval (CI), 7.2-12.4] and the mean overall survival (OS) was 49.4 weeks (95% CI, 30.1-68.8). The most common adverse reactions reported were skin reactions, including acne (67%), hand-foot syndrome (16.7%) and paronychia (16.7%), followed by hypocalcemia (50%), hypomagnesemia (16%), stomatitis (20%) and gastrointestinal disorders (12%). The results of the present single-center study demonstrated that cetuximab monotherapy is beneficial for the treatment of chemotherapy-refractory patients with mCRC and that it has an acceptable level of safety and manageable side-effects.

Feasibility study of docetaxel and cyclophosphamide six- cycle therapy as adjuvant chemotherapy for Japanese human epidermal growth factor receptor 2-negative breast cancer patients.

BACKGROUND: We compared treatment completion rates and safety of docetaxel and cyclophosphamide six- cycle therapy (TC6) with docetaxel followed by 5FU, epirubicin and cyclophosphamide (T-FEC) therapy in Japanese patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. MATERIALS AND METHODS: We administered TC6 q3w or T-FEC q3w to HER2-negative breast cancer patients. The primary endpoint of this trial was toxicity. As second endpoints, the treatment completion rate and relative dose intensity were evaluated. RESULTS: The TC6 and T-FEC group consisted of 22 and 21 patients, respectively. Concerning hematological toxicity, grade 3 or higher adverse reactions included neutropenia and febrile neutropenia. As non-hematological adverse events, exanthema and peripheral neuropathy were frequently reported in the TC6 group, whereas more patients of the T-FEC group reported nausea and vomiting. In TC6, the treatment completion rate was 86.4% and the relative dose intensity of docetaxel was 93.2%. In T-FEC, the values were 95.2% and 98.9%, respectively. CONCLUSIONS: These results suggest that TC6 is tolerable in Japanese, and that this regimen can also be performed in outpatient clinics. However, with the TC6 regimen, the compliance was slightly lower than with the T-FEC regimen, and supportive therapy needs to be managed appropriately.

Safety assessment of intravenous administration of trastuzumab in 100ml saline for the treatment of HER2- positive breast cancer patients.

BACKGROUND: The infusion rate is considered to affect incidence and severity of infusion reactions (IRs) caused by protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. In the study, we evaluated the safety of TRS intravenously administered over 30 minutes with 100 ml saline to reduce burden of patients, safety of infusion with 250 ml saline already being established. MATERIALS AND METHODS: Women with HER2 positive breast cancer, ≥18 years and ≥55% left ventricular ejection fraction (LVEF), were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS 100ml over 30 minutes in a three-week cycle. RESULTS: A total of 31 patients were recruited, 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients at the first dose. However, no IR was observed after reducing to 100 ml saline. No decrease of LVEF, increase of serum brain natriuretic peptide or any other adverse events were reported. CONCLUSIONS: Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients can be considered safe based on results from the study. It can be given on an outpatient basis as with the currently recommended dilution in 250 ml saline.

Pleomorphic lobular carcinoma in a male breast: a case report with review of the literature.

Invasive lobular carcinoma (ILC) is a distinct type of breast carcinoma and represents 5-15% of invasive breast carcinomas in female. However, the occurrence of ILC is exceptional in male breast, and the incidence is 1.5-1.9% of male breast carcinomas. Herein, we report a case of pleomorphic lobular carcinoma in a male breast. A 76-year-old Japanese male with a history of treatment with a progestational agent for prostate cancer presented with a right breast tumor. Magnetic resonance imaging showed gynecomastia of bilateral breasts and an irregular-shaped nodule in his right breast. Histopathological study revealed infiltrative neoplastic growth of discohesive tumor cells arranged in single-filed linear cords or trabeculae. These neoplastic cells had variable-sized large nuclei containing occasional nucleoli. Immunohistochemically, these tumor cells lacked E-cadherin expression. Accordingly, an ultimate diagnosis of pleomorphic lobular carcinoma was made. This is the third documented case of pleomorphic lobular carcinoma of male breast. Our analyses of the clinicopathological features of this type of tumor revealed that patients were middle-aged or elderly men, and all cases were free from lymph node metastases or recurrence. Gynecomastia and a history of hormonal agent intake were present only in the current case. The most commonly proposed risk factor for the development of male breast cancer is elevated level of estrogen, and a possible link between the development of male breast cancer and estrogen therapy for prostate cancer has been suggested. The clinicopathological features of ILC of male breast remains unclear; therefore, additional studies are needed to clarify them.

Feasibility and toxicity of docetaxel before or after fluorouracil, epirubicin and cyclophosphamide as adjuvant chemotherapy for early breast cancer.

BACKGROUND: The tolerance and safety associated with the administration order of the anthracycline and taxane drugs have not been evaluated. PATIENTS AND METHODS: Breast cancer patients with node-positive or high-risk patients with node-negative were eligible. The feasibility and toxicity were evaluated in the following regimens--arm A, 3 courses of fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) followed by 3 courses of docetaxel 100 mg/m(2) (DOC); arm B, 3 courses of DOC followed by 3 courses of FEC. RESULTS: Forty-two patients were registered. The relative dose intensity was 94.2 % for FEC and 97.8 % for DOC in arm A, and 98.9 % for DOC and 95.2 % for FEC in arm B. In arm A, grade 3 or higher hematological toxicity was observed in nine patients, and febrile neutropenia developed in three patients with FEC. In arm B, grade 3 or higher hematological toxicity was observed in seven patients, but febrile neutropenia was not noted in any patient. CONCLUSION: The regimens in both arms A and B were safe regarding adjuvant chemotherapy for early breast cancer. However, DOC followed by FEC might be more tolerable. Further studies will maximize the results obtained with DOC followed by FEC.

The Kampo medicine Goshajinkigan prevents neuropathy in breast cancer patients treated with docetaxel.

BACKGROUND: Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients. MATERIALS AND METHODS: Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 µg/day B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design. RESULTS: The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was 2.7 ± 2.2. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was 4.9 ± 2.4. CONCLUSIONS: Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen.