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Results for “Pathologic Complete Response”

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PubMed1986

Treatment of locally advanced breast cancer using primary induction chemotherapy with hormonal synchronization followed by radiation therapy with or without debulking surgery.

Fifty-one patients with stage IIIA or IIIB locally advanced breast cancer received primary induction chemotherapy (hormonal synchronization, 46 patients) to a maximum objective clinical response before proceeding to local therapy. Patients achieving a pathological complete response (CR) received radiation therapy, while patients with residual disease, partial response (PR), or stable disease (NC) received debulking surgery prior to radiation therapy; in all patients, 6 additional months of chemotherapy were administered. Chemotherapy consisted of cyclophosphamide (500 mg/m2 iv) and doxorubicin (30 mg/m2 iv) on day 1; tamoxifen (40 mg/m2 orally) on days 2-6; Premarin (0.625 mg/m2 orally) every 12 hours for three doses, beginning on day 7; and methotrexate (300 mg/m2 iv) followed in 1 hour by 5-fluorouracil (500 mg/m2 iv) on day 8 and leucovorin rescue (10 mg/m2 orally) every 6 hours for six doses, beginning 24 hours after methotrexate. Fifty patients are evaluable with respect to response, time to disease progression, and survival. The rate of objective response to chemotherapy was 90%; 52% of the patients had CR, 38% had PR, and 10% had NC. The median numbers of chemotherapy cycles to achieve CR, PR, and NC were five, four, and four, respectively. Twenty-four patients with CR to chemotherapy were pathologically assessed, 22 by multiple biopsies and 2 by mastectomy. Seventy-one percent of the patients were proven to have pathological CR. All patients completing combined therapy thus far are disease free. Nine of 29 patients with stage IIIB disease have relapsed; 7 of 23 with inflammatory histology have relapsed; and 2 of 20 with stage IIIA disease have relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

[Ovarian carcinoma: current therapeutic aspects. A review].

Ovarian cancer is the leading cause of gynaecologic cancer death and the fourth most frequent cause of cancer death in women. 70% of all ovarian cancers will be diagnosed only at an advanced stage of the disease despite the improvements in diagnostic tools. Standard therapeutic concepts and new therapeutic modalities are discussed. Staging laparotomy with cytoreductive surgery is the most important part of initial patient management. Second-look operation has recently come under criticism, as it probably offers only minor therapeutic benefit. However, it remains the golden rule for evaluating different therapy modalities in the setting of a clinical trial. After surgery, chemotherapy is indicated for all patients with ovarian cancer FIGO stage III and IV. The question whether all patients with stage I and II disease need additional treatment remains unresolved. The standard regimen for patients with advanced ovarian cancer consists of six months' chemotherapy with a combination of cisplatin and an alkylating agent. Current cisplatin containing regimens achieve a clinical response rate of 60-80% and a documented pathologic complete response rate of 30% overall. Despite higher overall response rates and increased disease-free survival rates with cisplatinum combinations, long term survival is not significantly altered. Investigative approaches with intraperitoneal chemotherapy, biologic response modifiers and drug resistance modifiers may open new therapeutic avenues for this challenging disease. Radiotherapy (open field technique) also represents a highly active and curative treatment modality for certain ovarian cancer patients. Nowadays radiotherapy is mainly used as adjuvant treatment for patients with low risk early stage disease and as consolidation treatment for patients with complete remission after chemotherapy and second-look operation.

Adult↗

PubMed1988

Preoperative combined modality therapy for stage III M0 non-small cell lung carcinoma.

More than 1/3 of all non-small cell lung carcinoma (NSCLC) patients present with locally advanced non-metastatic disease. Despite radiation therapy and surgery the survival of these patients remains poor. In an effort to improve upon these results 33 clinical Stage III M0 patients from April 1985 through September 1986 were entered into a Phase II study at Rush-Presbyterian-St. Luke's Medical Center. Treatment included 5-FU by continuous infusion, VP-16, cisplatin and concurrent split course radiation therapy followed by surgical resection when possible. The overall clinical response rate is 74%. Fifty-seven percent of the preoperative group of patients went to surgery with a 100% resectability rate. These patients had a 50% pathologic complete response with no tumor found in the resected specimen. All surgical margins were free of disease and there were no operative deaths. This concurrent combined modality therapy is feasible with the major toxicities being leukopenia, nausea, and vomiting. With an overall median follow-up of 15 months, 36% of the patients remain alive. Overall local control is 71%. Actuarial observed 2 yr. survival is 33% and the median survival is 15 months. Histologic complete response appears to be an early indicator of the efficacy of this treatment regime. With 83% of the resected pathologic complete responders alive without evidence of disease, this preoperative combined modality therapy offers an appealing approach.

Adenocarcinoma↗

PubMed1991

A comparison of hexamethylmelamine (altretamine), cyclophosphamide, doxorubicin, and cisplatin (H-CAP) vs. cyclophosphamide, doxorubicin, and cisplatin (CAP) in advanced ovarian cancer.

We retrospectively compared the results of treatment with hexamethylmelamine (HMM), cyclophosphamide, doxorubicin, and cisplatin (H-CAP) to treatment results using cyclophosphamide, doxorubicin, and cisplatin (CAP) in patients with advanced ovarian cancer. The treatments were identical in dosage and schedule with the exception of the addition of HMM to one regimen. Fifty-five patients treated with H-CAP between August 1977 and March 1980 were compared with a subsequent group of 22 patients who received CAP between October 1984 and October 1987. Following 6 months of therapy, patients were restaged either with second-look laparotomy or with clinical restaging. Fifty-three of 55 patients (96%) and 14/21 (67%) patients had objective responses to H-CAP and CAP respectively (p = 0.001). The pathologic complete response rate as determined by second-look laparotomy was higher in the patients who received H-CAP (35% vs. 19%). The median survival of patients receiving H-CAP is 47 months compared to 21 months for the CAP patients. In limited residual disease patients (maximum tumor diameter less than or equal to 3 cm), the median survival also favored the H-CAP treatment (101 months vs. 21 months, p = 0.002). The median time to progression was greater in patients receiving H-CAP vs. those receiving CAP (67 months vs. 16 months, p = 0.045). Treatment-related toxicity was similar for the two regimens. These findings suggest that the addition of HMM to CAP chemotherapy prolongs the median survival for patients with limited residual disease advanced ovarian cancer.

Altretamine↗

PubMed1986

A critical reassessment of second-look laparotomy in epithelial ovarian carcinoma.

Eighty-eight women with epithelial ovarian carcinoma, treated by first-line chemotherapy, achieved a complete clinical response and underwent second-look laparotomy to assess the true pathologic status of their disease. Persistent tumor was found in 50 patients (57%). Thirty-two of these (36%) had obvious gross tumor, whereas, 16 (18%) had microscopic disease. Thirty-eight patients (43%) had no pathologic evidence of persistent ovarian carcinoma. With a follow-up of 6 to 60 months, 30 of these patients (79%) remain without evidence of recurrence. Multivariate logistic regression analysis revealed three covariates that were independently significant in predicting continued disease-free status. These included: the greatest diameter of the largest residual tumor left at the primary operation; histologic features of the tumor; and the diameter of the largest tumor aggregate found at initial operation. A mathematical model based on the most significant covariates was designed to assess the relative risk of any patient having persistent tumor at second-look laparotomy. A comparison of the predicted to actual outcome revealed a sensitivity of the model of 88%, a specificity of 71%, and an accuracy of 77%. Second-look laparotomy represents the basis on which potentially curative second-line salvage therapy can be initiated. With an increasing period of follow-up and with greater numbers of patients, it can potentially document a complete pathologic response to first-line therapy administered with curative intent, and identify patients for additional, adjunctive therapy, who are at risk of recurrence.

Carcinoma↗

PubMed1991

Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.

One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.

Adult↗

PubMed1987

High-dose pulse chlorambucil in advanced, low-grade non-Hodgkin's lymphoma.

High-dose pulse chlorambucil was given orally at a dose of 16 mg/m2 daily for 5 consecutive days each month, as reported by Cadman et al. It was used to treat 33 patients with advanced, low-grade non-Hodgkin's lymphoma. With median follow-up of 4.2+ years, 70% of the patients achieved objective response. Eleven of 24 patients with follicular small cleaved cell lymphoma (FSCL) had pathological complete response; nine of 24 with FSCL and three of seven with small lymphocytic lymphoma had partial response. Median disease-free survival was 28 months. Actuarial survival for all patients was 60% at 5 years from initiation of therapy. Treatment toxicity was minimal. Pulse chlorambucil is an effective and minimally toxic palliative therapy for advanced FSCL.

Administration, Oral↗

PubMed1986

Intra-arterial chemotherapy as an adjuvant to surgery in transitional cell carcinoma of the bladder.

Regional chemotherapy with intra-arterial cis-platinum and doxorubicin as an adjuvant to total cystectomy and urinary diversion has been evaluated in a phase I to II study. In the first 17 patients chemotherapy consisted of 40 to 75 mg. per m. cis-platinum intra-arterially during 30 minutes, 30 to 40 mg. per m. doxorubicin intra-arterially during 60 minutes (11 patients) or 12 hours (6 patients) and 400 to 500 mg. per m. cyclophosphamide intravenously. The remaining 8 patients received 70 to 100 mg. per m. cis-platinum intra-arterially during 30 minutes. Intra-arterial chemotherapy was administered through a percutaneous catheter placed in the hypogastric artery before each course. Courses were repeated at 4-week intervals. A total of 25 patients received 58 courses (median 2 per patient). Clinical stages of disease in the patients entering the protocol were T3aNxMo (8), T3bNx-2Mo (12) and T4a-bNxMx-1 (5). Clinical response was assessed in 24 of 25 patients: 6 achieved a complete clinical response, 12 had a partial response and 7 had no response. Of 25 patients 16 underwent total cystectomy and urinary diversion with pathological staging as follows: ToNoMo in 3, T1NoMo in 1, T3aNoMo in 5, T3bNo-2Mo in 6 and T4NoMo in 1. Intra-arterial chemotherapy can produce a complete pathological response in patients with locally advanced bladder cancer and is tolerated well by most patients.

Aged↗

PubMed1990

High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer.

PURPOSE: To compare cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide as primary chemotherapy for stage III (suboptimal) and stage IV ovarian cancer. PATIENTS AND METHODS: Three hundred forty-two patients were randomly assigned to treatment with six courses of intravenous (i.v.) cisplatin 100 mg/m2 plus i.v. cyclophosphamide 600 mg/m2, or i.v. carboplatin 300 mg/m2 plus i.v. cyclophosphamide 600 mg/m2. RESULTS: The estimated median survivals were 17.4 and 20.0 months for the cisplatin and carboplatin study arms, respectively. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the P = .02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. Pathologic complete response rates were similar for both study arms. There was less thrombocytopenia on the cisplatin arm (P less than .001); however, there was less nausea and emesis (P less than or equal to .001 for courses 1 to 5), renal toxicity (P less than .001), anemia (P = .01), hearing loss (P less than .001), tinnitus (P = .01), neuromuscular toxicities (P = .001), and alopecia (P less than .001) on the carboplatin arm. CONCLUSION: Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.

Adult↗

PubMed1990

Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy.

Thymic carcinomas are rare malignant neoplasms of the thymic epithelium that are distinguished from the malignant thymomas by the presence of cytologic atypia. Thymic carcinomas may metastasize outside of the thorax and are associated with a very poor prognosis. Complete responses of thymic carcinoma to chemotherapy alone have not been reported. A 21-year-old man with metastatic undifferentiated carcinoma of probable thymic origin is presented who achieved a pathologic complete response with cisplatin, vinblastine, and bleomycin chemotherapy. Additional consolidative chemotherapy with cisplatin and etoposide was administered. The patient remains disease-free 5 years after diagnosis. Cisplatin, vinblastine, and bleomycin chemotherapy appears to have significant activity against thymic carcinoma.

Adult↗

PubMedDate not supplied

Alpha-fetoprotein in the management of germ cell tumors of the ovary.

From 1982 to 1989 positive alpha-fetoprotein (AFP) levels were detected after surgery in 3 patients with pure immature teratoma, 7 patients with mixed germ cell tumors and 16 patients with pure endodermal sinus tumor (EST) of the ovary. In the three patients with pure immature teratoma, AFP serum levels became spontaneously undetectable in one month without chemotherapy. The marker was thereafter negative, despite the persistence of tumor in 2 patients, and a relapse in the third one. The serum levels of AFP did not correlate with the stage of EST and mixed germ cell tumors. The monitoring of AFP serum levels during treatment correlated with response to chemotherapy: of the 16 patients with pure EST, 14 achieved a serological complete response and did not undergo second look surgery; two patients had a serological partial response. One of them reached a serological complete response after further chemotherapy. The other patient with liver extragonadic tumor underwent liver lobectomy with negative histology. Among 7 patients with mixed germ cell tumor, 6 achieved a serological and pathologic complete response. The 7th patient had a serological complete response, but microscopic residual tumor at second look laparotomy. The decrement curve of AFP was not predictive for recurrence. However, AFP monitoring was useful for an early diagnosis of relapse in 4 patients. AFP is a reliable marker for the diagnosis, treatment evaluation and follow-up of patients with pure EST and a useful marker in the clinical management of mixed germ cell tumors of the ovary.

Adolescent↗

PubMed1990

The role of hexamethylmelamine in the combination chemotherapy of advanced ovarian cancer: a comparison of hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (H-CAP) versus cyclophosphamide, doxorubicin, and cisplatin (CAP).

To evaluate the contribution of hexamethylmelamine (HMM) to the treatment of advanced ovarian cancer with combination chemotherapy, we compared the results of treatment with HMM, cyclophosphamide, doxorubicin, and cisplatin (H-CAP regimen) to treatment results using cyclophosphamide, doxorubicin, and cisplatin (CAP regimen). The treatment regimens were identical in dosage and schedule with the exception of the addition of HMM to one regimen. Fifty-five patients treated with H-CAP at Vanderbilt University Hospital between August 1977 and March 1980 were compared with a subsequent group of 22 patients who received CAP between October 1984 and October 1987. Following six months of therapy, patients were restaged either with second-look laparotomy or with clinical restaging. Fifty-three of 55 patients (96%) had objective responses to H-CAP compared with 14 of 21 patients (67%) treated with CAP (p = 0.001). The pathologic complete response rate was also higher in the patients who received H-CAP (35% versus 19%). The median survival of patients receiving H-CAP is 47 months compared to 21 months for the CAP patients. When patients with limited residual disease (maximum tumor diameter less than or equal to 3 cm) were compared, the median survival also favored the H-CAP treatment (101 months versus 21 months, p = 0.002). The median time to progression was also greater in patients receiving H-CAP versus those receiving CAP (67 months versus 16 months, p = 0.045). Treatment-related toxicity did not differ substantially between the two regimens. Our findings suggest that the addition of HMM to CAP chemotherapy prolongs the median survival in patients with ovarian cancer and limited residual disease following cytoreductive surgery.

Adult↗

PubMed1989

Neoadjuvant treatment of stages T2 to T4 bladder cancer with cis-platinum, cyclophosphamide and doxorubicin.

In an ongoing phase II study 17 patients with potentially operable transitional cell carcinoma of the bladder (stages T2 to T4, Nx, Mo) have been treated with intravenous cis-platinum (50 mg.per m.2), cyclophosphamide (400 mg.per m.2) and doxorubicin (40 mg.per m.2). They were to receive 3 treatments at 3-week intervals before cystectomy and 2 treatments at 3-week intervals commencing 5 weeks after cystectomy. Of 17 patients 14 (82 per cent) completed all 3 preoperative treatments but only 7 (41 per cent) continued on to complete the entire 5 treatments. In most cases incomplete therapy was due to patient refusal. Toxicity was low as measured by World Health Organization standards. Of the 17 patients 9 (53 per cent) exhibited objective tumor response (pathological downstaging or greater than 50 per cent reduction of tumor volume determined by either computerized tomography scan and/or endoscopic examination. When the determination was made by endoscopy the changes were dramatic and not borderline.) No patient demonstrated a pathological complete response. All 9 of the responders (100 per cent) remain clinically free of disease at a median follow-up of 19 months (range 4 to 30 months). The 8 nonresponders have done poorly with 5 dead of disease, 1 alive with pelvic recurrence and 2 free of disease at 4 and 12 months. These tumor response rates compare favorably with other cis-platinum-based combination regimens. The response to the chemotherapy appears to be an important prognostic indicator. Phase III trials must be conducted to determine whether this neoadjuvant chemotherapy regimen has a significant effect on long-term patient survival.

Aged↗

PubMed1991

Measurement of the ovarian cancer-associated antigen CA 125 in monitoring tumor burden and response to chemotherapy.

CA 125 serum levels were measured in 74 patients with ovarian carcinoma. Among 31 patients undergoing a second look laparotomy (SL) after chemotherapy pathologic complete response (PCR) was observed in 14 patients, residual disease (RD) less than 2 cm in 7 patients and RD greater than 2 cm in 10 patients. The disease status was compared to the CA 125 serum levels measured just before SL. Thirteen of the 14 patients with PCR had serum CA 125 values less than 35 U/ml (specificity: 93%). On the other hand, only 10 of the 17 patients with RD showed serum levels greater than 35 U/ml (sensitivity: 59%). Moreover, in the 43 patients receiving chemotherapy, CA 125 levels correlated with the course of the disease in 36 (84%). With regard to early detection of recurrence, in 9/14 patients with PCR, whose CA 125 levels were monitored monthly, by 1 to 7 months an increase of the tumor marker preceded clinical evidence of relapse in 9/9 relapses (100%). In conclusion, CA 125 assay can be helpful in the management of ovarian cancer patients, in monitoring the response to chemotherapy, in the early detection of tumor recurrence, and in predicting the SL findings, although the low sensitivity could be a major drawback in patients with RD before SL.

Adult↗

PubMed2026

Epigenetic Reactivation of TNFRSF19 Suppresses Mitophagy and Sensitizes Triple-Negative Breast Cancer to Doxorubicin.

Doxorubicin remains an important component of chemotherapy for triple-negative breast cancer (TNBC), yet chemoresistance severely limits its clinical efficacy. Here, we identify Tumor necrosis factor receptor superfamily member 19 (TNFRSF19) as an epigenetically silenced gene that critically regulates doxorubicin response. Integrative analyses of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and clinical cohorts reveal that high TNFRSF19 expression predicts superior pathological complete response and improved survival in doxorubicin-treated TNBC patients. Mechanistically, TNFRSF19 binds the kinase domain of TGFBR1 via its intracellular domain, disrupting TGFBR1-SMAD3 complex formation and thereby inhibiting SMAD3 phosphorylation, nuclear translocation, and transcriptional activation of PTEN-induced putative kinase 1 (PINK1). This suppresses PINK1/Parkin-mediated mitophagy, contributing to mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and amplified DNA damage upon doxorubicin treatment. Notably, TNFRSF19 is downregulated in TNBC due to DNA hypermethylation, and decitabine restores its expression via promoter demethylation, thereby enhancing the therapeutic efficacy of doxorubicin in vitro and in vivo. Collectively, these findings establish TNFRSF19 as a critical epigenetic regulator of mitophagy, highlighting its potential as a predictive biomarker for doxorubicin response and a therapeutic target for sensitizing TNBC to doxorubicin.

DNA methylation↗

PubMed2026

Integrated analysis reveals the impact of obesity on triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous breast cancer subtype with limited therapeutic options. While the prevalence of overweight/obese (OW/OB) women continues to rise, the impact of obesity on molecular features of TNBC remains incompletely understood. We investigated clinicopathological and molecular data (including genomic, transcriptomic, proteomic and metabolomic profiling) using our original multi-omics database of TNBC (N = 465) for associations with patient body mass index (BMI). Multi-omics profiling revealed that OW/OB patients exhibited worse survival as well as elevated inflammation of tumor microenvironment, higher expression of immune checkpoints, and dysregulated lipid metabolism. Our in vivo experiments demonstrated that tumors in obese mice displayed faster growth rates, a higher proportion of PD-1+CD8+ T cells and enhanced responsiveness to anti-PD-1 treatment. In addition, we analyzed data from four independent clinical trials and discovered that OW/OB patients demonstrated higher pathological complete response rates and longer progression-free survival following anti-PD-1-based immunotherapy. In conclusion, our study systematically revealed that obesity is associated with coordinated immune-metabolic remodeling in TNBC, characterized by checkpoint enrichment and lipid dysregulation, which may help explain the enhanced anti-PD-1 responsiveness and should be taken into account in the field of precision medicine.

Immunity↗

PubMed1990

Immunohistochemical analysis of P-glycoprotein expression correlated with chemotherapy resistance in locally advanced breast cancer.

We analyzed the expression of P-glycoprotein in samples from 48 patients with locally advanced breast cancer. Tumor samples from 40 patients were obtained at mastectomy, which was performed after three cycles of induction chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and prednisone. P-glycoprotein expression distributed focally was observed in 20 tumors by the immunoperoxidase method using the anti-p170-monoclonal antibody C219. The percentage of the tumor cell population expressing P-glycoprotein varied from less than 5% to greater than 30%; expression was observed significantly more often in tumors that showed less than partial response to the preoperative chemotherapy. Furthermore, P-glycoprotein was not expressed in eight tumor specimens obtained at the time of diagnosis, prior to chemotherapy, from patients who subsequently had pathologic complete responses. A comparative study of P-glycoprotein expression before and after chemotherapy and upon recurrence of tumor was done on a limited number of samples. No significant differences in P-glycoprotein expression were found. Therefore, it is possible that an intrinsic, rather than acquired, drug resistance may play a role in the failure of induction chemotherapy for locally advanced breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗