pirarubicin and Carcinoma--Ductal--Breast

It has been reported that expression levels of DNA repair genes are frequently associated with chemotherapy sensitivity and prognosis in breast cancer (BC) subtypes. The poly (ADP-ribose) polymerase-1 (PARP1), one of the major DNA single-strand break (SSBs) repair proteins, has been demonstrated a role in BC development. Because many of the chemotherapeutic agents target the tumor cell DNA, a DNA damage repair protein function is expected to impact therapeutic responses. However, the predictive effect of PARP1 in neoadjuvant chemotherapy (NC) treated BC is still controversial. To investigate whether PARP1 expression in BC is a possible biomarker to predict chemotherapeutic response, we assessed PARP1 expression in BC specimens based on collagen gel droplet embedded culture-drug sensitivity test (CD-DST) (in vitro) results and chemotherapeutic response of NC (in vivo). The surgical specimens from 108 patients with BC were recruited for CD-DST and PARP1 immunohistochemistry. We found that higher nuclear PARP1 (nPARP1) expression correlated with increased in vitro chemosensitivity against docetaxel (p=0.001) and epirubicin (p=0.022) based on CD-DST results. We also found that tumors with high nPARP1 expression were more sensitive to anthracycline/taxane based chemotherapy and associated with pathologic responses to NC using univariate and multivariate analyses (p=0.019 and p=0.037, respectively). Taken together, we conclude that nuclear expression of PARP1 is a useful marker to predict BC therapeutic responses.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Cyclophosphamide; Docetaxel; Doxorubicin; Drug Resistance, Neoplasm; Epirubicin; Female; Follow-Up Studies; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Logistic Models; Middle Aged; Neoadjuvant Therapy; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Retrospective Studies; Taxoids; Treatment Outcome

To evaluate the effect of anthracycline pirarubicin-based regimen in association with different ways of fluorouracil (5-Fu) as neoadjuvant and adjuvant chemotherapy for primary breast cancer.. Two hundred and eighty-nine primary breast cancer patients who were to be operated, two to eight cycles of pirarubicin in association with cyclophosphamide and 5-Fu (CTF or CTFci regimen) were given before operation. The pathological response rate, effect and its relation with the infusion routes of 5-Fu were analyzed.. The overall pathological complete remission (pCR) rate was 28.4%. The median follow-up period was 39 months. The 5-year DFS was 87.6% (95% CI:82.1% to 92.7%), 5-year DDFS was 89.9% (95% CI:84.0% to 95.8%), and overall survival was 99.6%. CTFci (5-Fu, continuous infusion) regimen was superior to CTF regimen in pCR rates (32.3% vs. 20.2%, P = 0.037), and 5-year DDFS were 92.9% and 80.1%, respectively (P = 0.015). The pCR group was superior to non-pCR group in 5-year DDFS (92.4% vs. 85.6%, P = 0. 033). The pCR rate of patients with ER/PR-positive tumor was significantly lower than those of ER/PR-negative (P = 0.004). The 5-year DDFS rates of HER-2 (+) and HER-2(-) groups were 75.0% and 91.9%, respectively (P = 0.043). In the ER/PR-positve group, the 5-year DDFS of CTFci regimen was superior to those of CTF regimen, 91.4% vs. 81.4% (P = 0.047).. CTF/CTFci regimen as neoadjuvant and adjuvant chemotherapy is effective for primary breast cancer. CTFci regimen is superior to CTF regimen in pathological complete response rate and 5-year DDFS. CTFci regimen may do better to ER/PR (+) patients' benefits compared with CTF regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Lymphatic Metastasis; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Proportional Hazards Models; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Remission Induction; Retrospective Studies; Survival Rate

A 53-year-old woman with left breast tumor was diagnosed as bilateral breast cancer(left; T3N3M0, Stage III C/right; T2N0M0, Stage II )in our hospital, both of which were revealed as invasive ductal carcinoma shown to be ER-negative, PgR negative and HER2-positive by core needle biopsy. In December 2004, paclitaxel and trastuzumab combination therapy was tried, but she went into shock just during administration of paclitaxel, and this therapy was discontinued. After that the triweekly CTF therapy was tried as an anthracycline containing regimen, and the lymph node metastases obtained a complete response after a month and a 38. 5% reduction of left primary breast tumor, which was the best response observed after three months. Time to progression was prolonged to 7 months(9 cycles). Although febrile neutropenia occurred in the first cycle, the therapy could be continued safely thereafter as an outpatient. Anthracycline-containing regimens are likely to be avoided because of the difficulty of combining with trastuzumab in the treatment of HER2 overexpressing advanced/metastatic breast cancer. But the CTF therapy of less cardiotoxicity and less alopecia, can expect longer use and better QOL as an alternative for HER2 overexpressing advanced/metastatic breast cancer patients.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Middle Aged; Paclitaxel; Receptor, ErbB-2; Shock

We report a case of good response to chemo-endocrine therapy with slight alopecia. A 55-year-old woman was diagnosed as advanced breast cancer with T4c, N3, M1, Stage IV, who was left cervical node-positive. She received 4 cycles of CTF (cyclophosphamide 100 mg/body/day 1-14, THP 30 mg/body/days 1,8, and 5-FU 750 mg/body/days 1, 8 4 wq) therapy in addition to oral tamoxifen (20 mg/body) administration. After this treatment, the primary tumor was markedly reduced (PR), and only slight alopecia was observed. Generally, 3 cycles of CAF (CEF) therapy induced severe alopecia (grade 3). But this CTF regimen caused grade 1 alopecia. Most women have strong resistance to alopecia. It seems that the quality of life for breast cancer patients was affected by the extent of the alopecia. Therefore, CTF therapy should be considered effective for advanced breast cancer patients while reducing the extent of alopecia.

Topics: Adenocarcinoma, Scirrhous; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Lymphatic Metastasis; Middle Aged; Quality of Life; Tamoxifen

We have investigated the usefulness of dual-isotope single photon emission computed tomography (SPECT) for predicting the response to chemotherapy in patients with breast cancer. Twenty-five patients with breast cancer were analyzed by SPECT using both 99m-technetium-tetrofosmin (99mTc-TF) and 201-thallium-chloride (201Tl). The relationship between response to chemotherapy and retention of each tracer was analyzed. 99mTc-TF retention was significantly higher in responders (42.0+/-37.9) than in non-responders (-11.3+/-34.6) (p=0.003). Ten of 13 patients (76.9%) with high 99mTc-TF retention (>15%) showed good response to chemotherapy, whereas 11 of 12 patients (91.7%) with low 99mTc-TF retention (<15%) did not respond to the therapy. The overall predictability to the response to chemotherapy was 84.0%. 201Tl retention (responders, 47.5+/-60.2% vs. non-responders, 55.8+/-45.0%; p=0.443) was not useful in therapeutic prediction, but was required to identify the lesion on the SPECT image. This is the first report to find that dual-isotope SPECT using 99mTc-TF and 201Tl is useful in predicting the response to chemotherapy in patients with breast cancer. Low 99mTc-TF retention is a strong predictor of therapeutic resistance, and high 99mTc-TF retention suggests a favorable response to chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Female; Humans; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Prognosis; Radiopharmaceuticals; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

A 59-year-old female complaining of breast tumor with suppurative discharge was diagnosed as having advanced breast cancer (T4cN3M1-StIV), with giant liver metastasis. Seven courses of combined chemoendocrine therapy (CTF + MPA) were used. Following the chemoendocrine therapy, primary tumor, lung, pleural, supraclavicular and parasternal metastasis disappeared, and the liver metastasis was obviously diminished. These effects continued for 1 year 7 months. Although CTF + MPA chemoendocrine therapy is widely used with advanced or recurrent breast cancer, a clearly effective case has almost never been reported. The reason for the remarkable effect in this case was the consistent immunity to breast cancer.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Medroxyprogesterone Acetate; Middle Aged

A 67-year-old advanced breast cancer patient with multiple bone metastases showed a remarkable response to the combination therapy of mitoxantrone (MIT) and medroxyprogesteron acetate (MPA) after failure of anthracycline therapy. Eight course of CTF (cyclophosphamide, THP-adriamycin, 5-fluorouracil) and subsequent 4'-epi-adriamycin were performed for locally advanced breast cancer and multiple bone metastases, but the ulcerated breast cancer enlarged. Then the combination therapy of MIT (10 mg/day) and MPA (1,200 mg/day) was carried out. Seven months after treatment, the ulcerated breast cancer disappeared completely and the serum levels of CA 15-3, TPA and CEA decreased within the normal range. These results suggest that combination therapy with mitoxantrone may well be effective against the anthracycline-resistant breast cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Doxorubicin; Drug Administration Schedule; Drug Resistance; Female; Humans; Medroxyprogesterone Acetate; Mitoxantrone