National Cancer Institute®
Last Modified: October 1, 2002
UI - 12016394
AU - Nishimura R; Nagao K; Miyayama H; Matsuda M; Baba K; Matsuoka Y;
TI - Yamashita H; Fukuda M An evaluation of predictive factors involved in clinical or pathological response to primary chemotherapy in advanced breast cancer.
SO - Breast Cancer 2002;9(2):145-52
AD - Department of Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505, Japan.
BACKGROUND: The usefulness of primary chemotherapy has been widely recognized and applied to routine clinical practice to improve prognosis by downstaging. Nevertheless, none of many trials has been able to show a positive effect of primary chemotherapy in terms of prognosis, and predictive factors of outcome have not been defined and are still under investigation. METHODS: Primary chemotherapy was given to 50 patients with advanced breast cancer. Predictive factors involved in clinical or pathological response to primary chemotherapy (3 cycles of CE(F) therapy ) were investigated. RESULTS: The response rate in all patients was 56.0% (CR: 3 patients PR: 25 patients) and 64.1% in patients without distant metastases. MIB-1 was related to the clinical response and EIC (extensive intraductal component) was related to the pathological response; the response was high in patients with EIC negative tumors. Responders had tumors with higher proliferative activity, which decreased significantly after chemotherapy. Patients with a decrease of more than 30% in proliferative activity after chemotherapy had significantly higher disease-free survival rates. CONCLUSION: The proliferative activity and EIC status were useful predictors of clinical or pathological response to primary chemotherapy. A decrease in proliferative activity by chemotherapy significantly correlated with clinical response and reflected a favorable prognosis. The number of patients benefiting from primary chemotherapy might steadily increase by detecting these predictive factors.
UI - 12016397
AU - Kinoshita J; Haga S; Shimizu T; Imamura H; Watanabe O; Nagumo H; Utada
TI - Y; Okabe T; Kimura K; Hirano A; Kajiwara T Monotherapy with paclitaxel as third-line chemotherapy against anthracycline-pretreated and docetaxel-refractory metastatic breast cancer.
SO - Breast Cancer 2002;9(2):166-9
AD - Department of Surgery, Tokyo Women's Medical University Daini Hospital, 2-1-10 Nishi-ogu, Arakawa-ku, Tokyo 116-8567, Japan. email@example.com
We describe a patient with anthracycline-pretreated and docetaxel-refractory metastatic breast cancer who achieved a complete response after third-line chemotherapy with paclitaxel. A 59-year-old woman underwent modified radical mastectomy for advanced cancer in her left breast after local arterial neoadjuvant chemotherapy with anthracycline. Postoperatively anthracycline-containing adjuvant therapy was administered. Pulmonary metastases occurred 15 months after surgery, which did not respond to 4 cycles of second-line chemotherapy with docetaxel, given at 60 mg/m(2) every 3 weeks. Therefore 210 mg/m(2) of paclitaxel was given every 3 weeks as third-line monotherapy and induced a complete response with grade 3 neutropenia and hair loss as the major adverse effects. We suggest that paclitaxel is potentially effective as third-line monotherapy for anthracycline-resistant and docetaxel-refractory metastatic breast cancer.
UI - 12016387
AU - Fukutomi T; Akashi-Tanaka S
TI - Prognostic and predictive factors in the adjuvant treatment of breast cancer.
SO - Breast Cancer 2002;9(2):95-9
AD - Breast Surgery Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
The selection of systemic adjuvant therapy should be based on the appropriate prognostic and predictive factors. The established prognostic factors currently used in cases of primary breast cancer include axillary lymph node involvement, histologic subtype, tumor size, nuclear or histologic grade, estrogen (ER) and progesterone receptor (PR) status and proliferative index. Adjuvant chemotherapy has had an impact on the management of node-positive breast cancer, while the St. Gallen recommendations were established for postoperative adjuvant therapy for node-negative breast cancer. However, there is some contention regarding the histological (or nuclear) grading systems among different pathologists. With regard to biological measurements, the most useful prognostic/predictive factors are hormone receptor status and HER-2 overexpression. ER and PR status can be used to establish the necessity of hormone therapy in the adjuvant setting. If the anti-HER-2 antibody and/or antiangiogenic agents are introduced into the adjuvant setting in the near future, determination of these factors is also recommended.
UI - 12172982
AU - Wenzel C; Locker GJ; Pluschnig U; Zielinski CC; Rudas M; Oberhuber G;
TI - Gnant MF; Taucher S; Jakesz R; Steger GG Phase I/II trial of weekly epidoxorubicin and docetaxel (wED) in the neoadjuvant and palliative treatment of patients with breast cancer.
SO - Cancer Chemother Pharmacol 2002 Aug;50(2):155-9
AD - Department of Internal Medicine I/Division of Oncology, University Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
PURPOSE: Anthracyclines and taxanes are the most active cytotoxic agents in the treatment of breast cancer. Based on observations with weekly administration of paclitaxel which results in better tolerability and higher dose intensity as compared with 3-weekly schedules, we designed a phase I/II trial with weekly epidoxorubicin and docetaxel (wED) for the preoperative and palliative treatment of patients with breast cancer. PATIENTS AND METHODS: A group of 33 female patients (20 neoadjuvant and 13 palliative) were treated with weekly epidoxorubicin (25-35 mg/m(2)) as a short i.v. infusion followed by docetaxel (25-40 mg/m(2)) as a 1-h i.v. infusion once a week for 6 weeks followed by 1 week off therapy, without G-CSF support. Sequential cohorts of patients were treated with epirubicin and docetaxel at the following dose levels: 25/25, 25/30, 30/30, 30/35, 35/35, and 35/40 mg/m(2). RESULTS: Patients received a total of 74 courses (median 2, range 1-4 courses) of this therapeutic regimen. The maximum tolerated dose occurred at the dose level combining 35 mg/m(2) of epidoxorubicin and 40 mg/m(2) of docetaxel, with the dose-limiting toxicity being neutropenic fever in two patients at dose level 6. CONCLUSIONS: The wED regimen is a feasible, safe, and highly active combination chemotherapy for advanced breast cancer. We recommend epidoxorubicin 30 mg/m(2) and docetaxel 35 mg/m(2) for further trials because of the high incidence of neutropenic fever and lymphocytopenia of WHO grade IV at dose levels 5 and 6.
UI - 12196717
AU - Inaji H; Komoike Y; Motomura K; Kasugai T; Sawai Y; Koizumi M; Nose T;
TI - Koyama H Breast-conserving treatment after neoadjuvant chemotherapy in large breast cancer.
SO - Breast Cancer 2002;9(1):20-5
AD - Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Japan.
Several recent trials have demonstrated that neoadjuvant chemotherapy can allow more patients to successfully undergo breast-conserving treatment (BCT), and does not confer a survival disadvantage compared with standard adjuvant chemotherapy. In addition, the pathological response of primary breast tumors to neoadjuvant chemotherapy appears to be a surrogate marker for patient outcome. In our series, during the 3.1 and 6.0 cm in diameter received epirubicin-based neoadjuvant chemotherapy. There were 55 (64.0%) responders and ultimately 64 patients (74.4%) were treated with BCT. The margin positive rate was 14.1%(9/64), similar to the rate after BCT for early-stage breast cancers, the largest diameter of which was smaller than 3 cm. At a median follow-up of 30 months, only 3 patients in the BCT group have developed local recurrence; the local recurrence rate appears to be comparable to that after BCT for early stage breast cancers. Long term follow-up is required, however, to establish whether this procedure is a safe alternative to mastectomy for patients with large breast cancers.
UI - 12196726
AU - Matsuo K; Fukutomi T; Watanabe T; Hasegawa T; Tsuda H; Akashi-Tanaka S
TI - Concordance in pathological response to neoadjuvant chemotherapy between invasive and noninvasive components of primary breast carcinomas.
SO - Breast Cancer 2002;9(1):75-81
AD - Department of Surgical Oncology, National Cancer Center Hospital, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
BACKGROUND: Invasive breast carcinomas are composed of invasive and noninvasive components in varying proportions and sometimes the two components show different histopathological responses to chemotherapy, however there has been no study as yet comparing the pathological response to chemotherapy of invasive and noninvasive components. PATIENTS AND METHODS: A consecutive series of 100 women neoadjuvant chemotherapy with doxorubicin and docetaxel every three weeks before surgery. After the chemotherapy, surgically resected specimens were studied histologically according to the criteria of the Japanese Breast Cancer Society. RESULTS: Five cases (5/100; 5%) were determined to show Grade 3 pathological response, and 28 cases (28/100; 28%) showed Grade 2 response. There were 6 Grade 3 (6/96; 6%) and 18 Grade 2 (18/96; 19%) invasive component cases. There were 7 Grade 3 (7/82; 9%) and 18 Grade 2 (18/82; 22%) cases showing pathological response in the noninvasive component. With regard to pathological response, there was a strong correlation between the invasive and noninvasive components (p<0.001). There was also a correlation in pathological response between the invasive component and axillary lymph nodes in individual cases (p=0.02). There was no correlation between the response of the noninvasive component and axillary lymph nodes. By multivariate analysis, the overall primary tumor response was reflected by the histological response of the invasive component in the primary breast carcinoma. CONCLUSION: We suggest that the pathological response of the invasive component of breast carcinoma should be evaluated, which might provide more accurate information for prognosis and treatment decisions.
UI - 12196715
AU - Ikeda T; Jinno H; Matsu A; Masamura S; Kitajima M
TI - The role of neoadjuvant chemotherapy for breast cancer treatment.
SO - Breast Cancer 2002;9(1):8-14
AD - Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. firstname.lastname@example.org
Neoadjuvant chemotherapy has become popular, especially for patients with advanced breast cancer. The pros and cons of neoadjuvant chemotherapy for treating breast cancer patients are reviewed. The advantages of neoadjuvant chemotherapy are 1) overall survival and recurrence-free survival rate are the same as post-operative chemotherapy, 2) serves as an in vivo sensitivity test, 3) increases the rate of breast conserving therapy, 4) facilitates the study of cancer biology. On the other hand, the disadvantages of neoadjuvant chemotherapy are 1) it modifies the stage, 2) treatment delay of PD cases, 3) residual intraductal component may be left behind after breast conserving surgery, 4) there are some cases of over-treatment. Combination chemotherapy is one possible way to increase the pathological CR rate, although the optimal order and cycles have not been determined. To avoid residual cancer cells after breast conserving surgery, the shrinkage pattern should be evaluated by MRI. Core needle biopsy should be performed before neoadjuvant chemotherapy to avoid over-treatment. It is essential to develop more effective regimens and stratify patients based on predictive factors.
UI - 12240628
AU - Mhawech P; Vlastos AT; Pelte MF
TI - Pathologic quiz case. Uterine polypoid mass in a postmenopausal patient following tamoxifen treatment for breast cancer.
SO - Arch Pathol Lab Med 2002 Sep;126(9):1125-6
AD - Department of Pathology, Geneva University Hospital, Switzerland.
UI - 12240546
AU - Thames HD; Petersen C; Petersen S; Nieder C; Baumann M
TI - Immunohistochemically detected p53 mutations in epithelial tumors and results of treatment with chemotherapy and radiotherapy. A treatment-specific overview of the clinical data.
SO - Strahlenther Onkol 2002 Aug;178(8):411-21
AD - Department of Biomathematics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
BACKGROUND: The aim was to ascertain whether many hundreds of clinical reports over the last decade are consistent with the prediction of a poorer outcome in cancer patients with p53 abnormalities treated with cytotoxic drugs and radiation. MATERIAL AND METHOD: There are 301 studies on the influence of p53 overexpression published through summer 2000, in which chemotherapy or radiotherapy was used alone or in combination with surgery. From 45 reports meeting stringent selection rules, comparison groups are identified in whom the same measure of outcome was reported for the same treatment applied to the same tumor, with results corrected for important prognostic factors. Metaanalysis techniques are then applied to the comparison groups. Attention was limited to reports using immunohistochemical techniques, to form comparison groups of sufficient size. RESULTS: Four comparison groups were identified by treatment and endpoint: 1) Stage I-III breast cancer (surgery and chemotherapy, disease-free survival, seven studies); 2) stage I-III breast cancer (surgery and chemotherapy, overall survival, six studies); 3) stage II-IV head and neck cancer (radiotherapy and chemotherapy, overall survival, five studies); 4) FIGO I-IV ovarian cancer (surgery and chemotherapy, overall survival, six studies). In the breast (disease-free survival) and ovarian (overall survival) comparison groups, the hazard ratio for a deleterious effect of p53 overexpression was significant or marginally significant, depending on assumed ranges for unreported hazard ratios in non-significant studies. CONCLUSIONS: Despite the many caveats related to metaanalysis applied to retrospective data, high variability of immunohistochemical technique, etc., a nearly significant negative effect of p53 overexpression on outcome of treatment with cytotoxic drugs and radiation emerges in the few studies where heterogeneity can be sufficiently reduced or accounted for.
UI - 7367722
AU - Mouridsen HT; Palshof T
TI - Principles and indications of endocrine treatment of advanced breast cancer.
SO - Recent Results Cancer Res 1980;71():112-7
The numerous trials that have been conducted in advanced breast cancer in premenopausal and postmenopausal women have increased the empiric basis for systemic cytotoxic and endocrine treatment. The treatment results have improved but are still very unsatisfactory, and with all the drugs now at our disposal many questions are still unanswered. For instant this applies to the optimal composition and scheduling of endocrine treatment, cytotoxic treatment, and combinations of these two treatments. During recent years the results of experimental studies have expanded our knowledge of the biology of breast cancer. Future clinical trials should be designed to test and use this information gained from basic research with the aim of improving the rational basis of treatment and obtaining better treatment results in advanced breast cancer.
UI - 6988911
AU - Rose C; Thorpe SM; Lober J; Daenfeldt JL; Palshof T; Mouridsen HT
TI - Therapeutic effect of tamoxifen related to estrogen receptor level.
SO - Recent Results Cancer Res 1980;71():134-41
Cytoplasmic oestrogen receptor (ER) determinations were performed in 59 postmenopausal patients with metastatic breast cancer. Fifty percent of the patients were found to be ER+. Forty patients were treated with tamoxifen (TAM) and 19 patients were treated with tamoxifen plus medroxyprogesterone acetate (MPA). The response rate of TAM-treated patients was 30% (12/40). Of the 21 ER+ patients, ten (48%) responded to therapy. The ER values of these patients were significantly higher than the ER values of nonresponders (P less than 0.01). No correlation could be found between the ER value and the duration of remission in TAM-treated patients.
UI - 7367728
AU - Lippman ME; Allegra JC
TI - Lack of estrogen receptor associated with an increased response rate to cytotoxic chemotherapy in metastatic breast cancer?
SO - Recent Results Cancer Res 1980;71():155-61
UI - 6988913
AU - Mouridsen HT; Palshof T; Rose C
TI - Therapeutic effect of tamoxifen alone versus tamoxifen in combination wtih gestagen and oestrogen in advanced breast cancer.
SO - Recent Results Cancer Res 1980;71():169-77
UI - 7388801
AU - DeWys WD; Allegra JC; Simon R; Lippman MB
TI - A proposed model for the prediction of response to endocrine therapy in breast cancer from the estrogen receptor status of one site and the number of metastatic sites.
SO - Cancer Res 1980 Jul;40(7):2423-7
A mathematical model for prediction of response to endocrine therapy of breast cancer has been developed based on a clonal concept of metastatic spread. The model includes an expression of the likelihood of response of an estrogen receptor-positive site and an expression of the concordance of receptor assays when multiple sites are assayed. Both of these are raised to a power function based on the number of sites of metastases to yield a predicted response rate. An excellent fit of the predictions of this mathematical model and response data from a series of patients receiving endocrine therapy was observed. This model provides a worthwhile insight into the biology of response to endocrine therapy. The model may be extended and refined through additional analyses.
UI - 7399477
AU - McGuire WL
TI - Steroid receptors and breast cancer.
SO - Hosp Pract 1980 Apr;15(4):83-8
Endocrine therapy can significantly prolong life in about a third of patients with advanced mammary carcinoma, but until recently it has been impossible to predict which ones. Assays for receptors specific for estrogen and progesterone have made the predictive process more accurate, and antiestrogens are providing the basis for a new approach to therapy. Clinical applications are outlined.
UI - 7414710
AU - Di Pietro S; Rovini D; Luini A; Muscolino G; Viganotti G
TI - Thermal gradient and response to estrogens or antiestrogens in advanced breast cancer.
SO - Tumori 1980 Aug 31;66(4):459-65
The correlations between the thermal gradient of superficial breast cancer lesions (before and 15 days after starting treatment) and the end results of hormonal therapies with estrogen and antiestrogens were investigated. Forty-four women with a median age of over 70 with locally advanced breast cancer and/or metastases mainly located in soft tissues entered the study. Twenty-two patients were treated with diethylstilbestrol sodium diphosphate (20 mg/day i.m.) and the other 22 with tamoxifen (20 mg/day orally). The initial iperthermia was reduced after 15 days in more than 50% of the cases and remained stationary in the others. The cases with a thermal gradient more than 2 degrees C of the tumors did better, in terms of remission, following therapy (64.7% versus 37.0%. However, an early decrease of the same gradient in the course of therapy appears scantily related to the response. The therapeutic results in the 2 groups were very similar: 45.5% complete or partial regression, with a median duration of more than 8 months, in those treated with diethylstilbestrol and 50%, with a median duration of more than 11 month, in those treated with tamoxifen. Only in some cases of the first group of patients the treatment was discontinued due to severe side effects.
UI - 7454090
AU - Bernardo-Strada MR; Imparato E; Aspesi G; Pavesi L; Robustelli Della
TI - Cuna G [Oral high doses of medroxyprogesterone acetate (MPA) in the treatment of advanced phases of breast and endometrial cancer]
SO - Minerva Med 1980 Nov 10;71(44):3241-6
The results of a pilot study on the use of oral medroxyprogesterone acetate (Provera-Upjohn) at high dose in a series of 50 consecutive women with advanced breast (30 cases) and endometrial carcinoma (20 cases) are reported. Patients with progressive disease, non liable to further conventional treatments, received MPA (500 mg/day orally) for 90 days. The evaluation of results have shown only partial responses: in 9/30 (30%) of women with disseminated breast carcinoma (median duration of response 10 months, median survival 15 months), and in 6/20 (30%) of patients with advanced endometrial carcinoma (median duration of response 15 months, median survival not reached at 28 months of follow-up). Even if with a lower response rate, as compared to the results obtained with parenteral formulation, the oral MPA maintains its therapeutic effectiveness in these hormonodependent tumors: easy to handle during the long term treatments, oral MPA could be a useful alternative also for maintenance therapy.
UI - 7455895
AU - Paone JF; Abeloff MD; Ettinger DS; Arnold EA; Baker RR
TI - The correlation of estrogen and progesterone receptor levels with response to chemotherapy for advanced carcinoma of the breast.
SO - Surg Gynecol Obstet 1981 Jan;152(1):70-4
Estrogen and progesterone receptor levels were determined simultaneously in tumor samples obtained from 105 patients who subsequently received a trial of hormonal or chemotherapy for metastatic carcinoma of the breast. Twenty-three of 33 estrogen receptor positive patients in contrast with three of 22 estrogen receptor negative patients achieved an objective response to hormonal therapy. More significantly, it was found that 12 of 16 estrogen receptor positive patients compared with only six of 34 estrogen receptor negative patients responded to combination chemotherapy. Simultaneous measurement of progesterone receptor improved the selection of tumors responsive to chemotherapy, as only four of 30 patients who were estrogen receptor negative-progesterone receptor negative achieved a response. Furthermore, the cumulative survival time of 36 months after the first recurrence of carcinoma of the breast was significantly lower in estrogen receptor negative patients receiving chemotherapy. These data indicate that patients with estrogen receptor negative carcinoma of the breast are resistant to standard hormonal and chemotherapeutic measures for metastatic disease and carry a poor prognosis.
UI - 7226163
AU - Pellegrini A; Massidda B; Mascia V; Ionta MT; Lippi MG; Muggiano A;
TI - Carboni E; Robustelli della Cuna G; Bernardo G; Strada MR; Pavesi L Ethinyl estradiol and medroxyprogesterone treatment in advanced breast cancer: a pilot study.
SO - Cancer Treat Rep 1981 Jan-Feb;65(1-2):135-6
Twenty patients with disseminated breast cancer unresponsive to conventional chemotherapy and chemohormonotherapy were treated with an alternating sequential schedule of ethinyl estradiol and medroxyprogesterone on the basis of correlations between hormones and estrogen and progestin receptors. Of 19 evaluable patients, six underwent partial or complete remission, while five others showed minor responses.
UI - 11956611
AU - Hamada N; Ogawa Y; Nishioka A; Kariya S; Terashima M; Yoshida S; Tochika
TI - N; Tanaka Y; Kumon M; Inomata T Breast-conservation treatment for bilateral breast cancer in five Japanese women.
SO - Oncol Rep 2002 May-Jun;9(3):469-74
AD - Department of Radiology, Hosogi Hospital, Kochi 780-8535, Japan. (BCT) was performed in 250 of 256 breast cancer patients. Five of the 250 patients had bilateral breast cancer, and 4 with synchronous bilateral breast cancer of the 5 were concomitantly treated by chemo-endocrine therapy before simultaneous breast-conservation surgery for bilateral breast cancer. Chemotherapy was performed using cyclophosphamide, pirarubicin, and 5-fluorouracil, while endocrine therapy was performed using an antiestrogen agent (tamoxifen or toremifene). All patients were also treated by radiotherapy. Since no severe side effects or complications were induced by these therapeutic approaches, bilateral breast cancer may be successfully treated by BCT as in unilateral breast cancer. However, of the 5 patients with bilateral breast cancer, cancer recurrence in the axillary lymph nodes was detected only in 1 patient with T2N1 cancer 78 months after simultaneous breast-conservation surgery for bilateral breast cancer.
UI - 11956612
AU - Hamada N; Ogawa Y; Nishioka A; Kariya S; Terashima M; Yoshida S; Tanaka
TI - Y; Inomata T An elderly patient with DCIS of the breast effectively treated with toremifene alone.
SO - Oncol Rep 2002 May-Jun;9(3):475-8
AD - Department of Radiology, Hosogi Hospital, Kochi 780-8535, Japan.
An elderly patient with breast cancer received toremifene monotherapy for one year, and about 60% tumor remission rate was obtained. Since viability of the residual tumor was suspected on ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI), lumpectomy was performed under local anesthesia. The histopathological diagnosis was ductal carcinoma in situ (DCIS). The patient did not undergo axillary lymph node dissection or systemic chemotherapy. The patient is alive without disease under postoperative radiotherapy and toremifene treatment. Toremifene monotherapy and/or preoperative adjuvant therapy with toremifene alone may be useful methods for elderly patients with breast cancer considering the patients' quality of life.
UI - 12173004
AU - Oshima H; Miyagawa H; Sato Y; Satake M; Shiraki N; Nishikawa H; Arakawa
TI - A; Ogino H; Hara M Adenofibroma of the endometrium after tamoxifen therapy for breast cancer: MR findings.
SO - Abdom Imaging 2002 Sep-Oct;27(5):592-4
AD - Department of Radiology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
We report a case of adenofibroma of the endometrium in a 69-year-old woman. This patient was receiving tamoxifen therapy after surgery for breast cancer. Magnetic resonance imaging showed an intracavitary mass containing multiple cystic components. We suggest adenofibroma as a possible diagnosis in cases of uterine masses with multiple cystic components and no clinical evidence of malignancy.
UI - 12235869
AU - Aoyama Y
TI - Experimental studies on the effects of the combined use of N-(4-hydroxyphenyl)retinamide (4-HPR) and tamoxifen (TAM) for estrogen receptor (ER)-negative breast cancer.
SO - Kurume Med J 2002;49(1-2):27-33
AD - Department of Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan.
We investigated the effects of combination therapy with N-(4-hydroxyphenyl)retinamide (4-HPR) and tamoxifen (TAM) on estrogen receptor (ER) negative breast cancer, for which no effective supplementary therapy has been established, using the human breast cancer cell line MDA-MB-231. TAM or 4-HPR alone had little antitumor effect, but the combined use of TAM and 4-HPR had a strong cell growth inhibitory effect. Cell cycle analysis by flow cytometry showed an increased frequency of the G2/M phases in the 4-HPR-TAM combination group. Measurement of 3H-TAM incorporation into the cell showed that, compared with the TAM group, the 4-HPR-TAM combination group incorporated about 1.45 times more TAM into the cell. Thin-layer chromatographic analysis of changes in the cell membrane ganglioside GM3 showed a marked increase in GM3 in the 4-HPR-TAM combination group. We speculate that the administration of TAM in the presence of 4-HPR changes the membrane glycolipid GM3, increasing intracellular TAM concentrations, thus exerting antitumor activity. Presumably, during this process, antitumor effects do not induce cell death but arrest the cell cycle in the G2 phase. Thus, the combined use of TAM and 4-HPR inhibited the growth of the ER-negative breast cancer cell line MDA-MB-231. These results suggest that combination therapy with TAM and 4-HPR can be a potent supplementary therapy also for ER-negative patients in clinical practice.
UI - 12296544
AU - Lindley C
TI - Developments in breast cancer therapy.
SO - J Am Pharm Assoc (Wash) 2002 Sep-Oct;42(5 Suppl 1):S30-1
AD - University of North Carolina School of Pharmacy, Chapel Hill, USA.
The lifetime risk of breast cancer in women is 1 in 8, with an increasing incidence in each decade of life after age 40. Breast cancer is considered curable with detection and treatment during Stages I and II, but disease-free survival drops in Stage III and is essentially zero in Stage IV. Breast-conserving surgical removal of tumors has been the standard of care for primary local therapy for more than a decade. For prevention of recurrence, tamoxifen is recommended in dosages of 20 mg/day for 5 years. The aromatase inhibitors are now considered first-line therapy in metastatic disease, and use of the monoclonal antibody trastuzumab has increased 5-year survival rates.
UI - 12202979
AU - Nabholtz JM; Reese D; Lindsay MA; Riva A
TI - Evidence for the use of chemotherapy in breast cancer.
SO - Int J Clin Oncol 2002 Aug;7(4):254-64
AD - Cancer Therapy Development Program and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA. email@example.com
Several distinct historical phases mark the evolution of chemotherapy for breast cancer, including the introduction of single agents in the 1960s, the development of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based regimens in the 1970s, the evaluation of the anthracyclines in the 1980s, and the incorporation of the taxanes in the 1990s. The greatest benefit from the use of standard combination chemotherapy occurs in the adjuvant setting, where absolute improvements in overall survival on the order of 10% have been achieved. In contrast, advances have been more modest in the treatment of metastatic disease, and novel agents and regimens are required for further progress. Of the new cytotoxic drugs introduced in the past decade, the taxanes and capecitabine appear to be the most promising, and have demonstrated activity alone and in combination for the treatment of metastatic disease. The introduction of trastuzumab, an antibody directed against the HER2 receptor protein, heralded the birth of targeted molecular therapy against breast cancer. It is clear that in the near future the further evaluation of trastuzumab combinations and the development of additional molecular agents will propel clinical breast cancer research. One of the main challenges of the new era will be identifying and validating predictive factors so that therapy may be individualized based on tumor biology, rather than empirically selected.
UI - 12202980
AU - Lonning PE
TI - The role of aromatase inactivators in the treatment of breast cancer.
SO - Int J Clin Oncol 2002 Aug;7(4):265-70
AD - Department of Oncology, Haukeland Hospital, University of Bergen, N - 5021 Bergen, Norway. firstname.lastname@example.org
Third-generation aromatase inhibitors and inactivators have earned their place in the treatment of metastatic breast cancer. The third-generation aromatase inactivator exemestane was found to be superior to megestrol acetate as second-line endocrine therapy in postmenopausal women, with respect to time to progression as well as overall survival, and the results from an ongoing study comparing exemestane with tamoxifen in first-line treatment are promising. The finding that exemestane may also work in patients previously exposed to nonsteroidal aromatase inhibitors reveals lack of complete cross-resistance between the compounds. Currently, exemestane given as monotherapy, or in sequence with tamoxifen (2-3 + 3-2 years of tamoxifen-exemestane or 5 years of tamoxifen followed by 2 years of exemestane) is being compared with tamoxifen 5 years monotherapy in the adjuvant setting. In addition, we are currently addressing the toxicity of exemestane in a placebo-controlled trial in low-risk breast-cancer patients. The results from these studies will outline the potential role of exemestane in adjuvant treatment and, potentially, for breast-cancer prevention in postmenopausal women.
UI - 12355936
AU - Ikeda T; Jinno H; Matsui A; Mitsui Y; Asaga S; Muto T; Wada M; Kitajima
TI - M [Breast cancer]
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1509-15
AD - Department of Surgery, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Adjuvant chemo-endocrine therapy for breast cancer (ACETBC) trial has been the first large scaled clinical trial performed in Japan. Several prospective randomized trials have been performed in Japan since ACETBC-1 trial started in 1985. The effect of oral 5-FU agents had been tested in prospective randomized trials and the statistically marginal effect of oral 5-FU agents in adjuvant settings has been reported. Several trials having CMF as a control arm started in 1996 when CMF combination chemotherapy was approved by the government. The results of these trials have not been published. To perform good clinical trials, it is imperative to construct infrastructures including clinical research coordinator, and abolish governmental regulation of the dose of anticancer agents.
UI - 12355946
AU - Sakurai T; Oura S; Kinoshita T; Yokochi H; Enomoto K; Nishimura M;
TI - Okamura Y [Advanced breast cancer with lung and pleural metastases responsive to anastrozole--a case report]
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1607-10
AD - Dept. of Surgery, Koyo Hospital.
A 63-year-old postmenopausal woman was referred to our hospital for treatment of ER positive advanced breast cancer. The patient had lung and pleural metastases with pleural effusion from breast cancer. She was treated with anastrozole, a 3rd-generation aromatase inhibitor, which brought about a marked regression of the lung tumor, and disappearance of pleural effusion. The patient experienced no adverse effects with this therapy. Anastrozole therapy is a useful treatment for postmenopausal women with ER positive advanced breast cancer.
UI - 12355948
AU - Chishima Y; Satou Y; Takano S; Kitajima A; Okamoto H; Aida Y; Noro M
TI - [Patient with bone metastasis of breast cancer who were improved by weekly DXR/TXT therapy]
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1615-9
AD - Dept. of Surgery, Sagamihara Kyoudou Hospital.
The patient was a 57-year-old female with the main complaint of left chest pain and gait disturbance. Multiple bone metastases were observed in the vertebral and pelvic bone. Pathological pressure fracture, stegnosis of the spinal canal and edematous changes in the spinal nerves, especially in the 4th and 5th thoracic vertebrae, were observed. The clinical pathological status was T4cN1M1b, OSS Stage IV. After 4 cycles of weekly doxorubicin (DXR) (20 mg/body)/docetaxel (TXT) (40 mg/body) therapy (day 1, day 8, day 15, 1-week recovery period) were given to the patient, CA15-3 had decreased from 1,200 U/ml to 28 U/ml. The histopathological effect was judged to be Grade 2. Thereafter, ICTP was increased to 12.7 ng/ml and after 2 cycles of the weekly DXR/TXT therapy (day 1, day 8, 2-week recovery period) had been added, the patient was able to walk. MRI of the thoracic vertebrae showed that the foci of bone metastasis had improved 9 months after the treatment with chemotherapeutics, and good PS was maintained. No serious adverse reactions were observed with the weekly DXR/TXT therapy. Therefore, weekly DXR/TXT therapy is considered to be effective in treating patients with bone metastasis.
UI - 12355960
AU - Street JC; Taguchi T
TI - Meeting highlights 38th annual meeting of the American Society of Clinical Oncology. Advances in adjuvant chemotherapy for management of breast cancer: the emerging role of docetaxel.
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1689-92
AD - Japan Society for Canser Chemotherapy, Osaka, Japan.
UI - 12104076
AU - Wu JT
TI - C-erbB2 oncoprotein and its soluble ectodomain: a new potential tumor marker for prognosis early detection and monitoring patients undergoing Herceptin treatment.
SO - Clin Chim Acta 2002 Aug;322(1-2):11-9
AD - Department of Pathology and ARUP, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA. email@example.com
c-erbB-2 oncoprotein (or p185) coded by c-erbB-2 oncogene can be extracted with detergent from cell membrane of breast tissue and breast tumor cell line. The ectodomain of p185 can be cleaved proteolytically from the transmembrane receptor and released into solution. In blood circulation, only the ectodomain can be found, whereas only p185 exists in the extracts of tissue and cell line. p185 can also be quantified in the fine-needle aspirate biopsies and the concentration of p185 from the biopsies of malignant breast tissue is much higher than that of the normal and benign tissue. Measuring the ectodomain of the c-erbB-2 oncoprotein not only is useful to identify breast cancer patient who will benefit from Herceptin treatment but also can be used to monitor patients during the treatment. Overexpression of p185 and the elevation of circulating ectodomain is usually associated with poor prognosis. Overexpression of p185 in breast cancer patients with positive estrogen receptor identifies a subgroup of patients who will not respond to the endocrine therapy. Activation of p185 appears to be an early event in tumorigenesis for some cancers. It is possible that the ectodomain could be used as an early tumor marker detecting benign disease. Copyright 2002 Elsevier Science B.V.
UI - 12181497
AU - de Jong N; Courtens AM; Abu-Saad HH; Schouten HC
TI - Fatigue in patients with breast cancer receiving adjuvant chemotherapy: a review of the literature.
SO - Cancer Nurs 2002 Aug;25(4):283-97; quiz 298-9
AD - University of Maastricht, Department of Health Care Studies, The Netherlands. firstname.lastname@example.org
The aim of this literature review was to evaluate the prevalence and course of fatigue in patients with breast cancer undergoing adjuvant chemotherapy and to examine factors relating to fatigue. Fatigue is one of the most common side effects of chemotherapy. High and fluctuating prevalence rates of fatigue have been found not only during but also after adjuvant chemotherapy. The intensity of fatigue seems to be stable throughout the treatment cycles, despite the common perception that more chemotherapy treatments lead to greater fatigue. The first two days after a chemotherapy treatment seem to be the worst period.The influence of factors such as pain, impaired quality of sleep, and depression are be highly consistent across several studies, although it is often not clear whether it is the symptoms that cause the fatigue or vice versa. The outcomes of the studies indicate that several symptoms are interrelated in a network of symptoms. Factors such as changes in weight, menopausal symptoms, coping, social support, and biochemical changes have been mentioned in the literature as potentially contributing to fatigue. Results have been conflicting and need further study.
UI - 12195757
AU - Baltali E; Altundag MK; Guler N; Ozisik Y; Firat D; Baran I; Tekuzman G
TI - Paclitaxel and doxorubicin combination in the first-line treatment of metastatic breast cancer.
SO - Tumori 2002 May-Jun;88(3):200-3
AD - Hacettepe University, Institute of Oncology, Department of Medical Oncology, 06100-Sihhiye, Ankara, Turkey.
Anthracyclines and taxanes are currently the most effective drugs in the treatment of metastatic breast carcinoma. The aim of this study was to determine the efficacy and toxicity of paclitaxel and doxorubicin combination in the first-line treatment of metastatic breast cancer. Forty-five women with metastatic breast cancer were recruited in the study. Median age was 49 years (range, 33-70). Treatment protocol: doxorubicin (50 mg/m2/day, 30-min infusion) followed by paclitaxel (200 mg/m2/day, 3-hr infusion) every 3 weeks. Response rates included complete response in 13 (28.9%) patients and partial response in 19 (42.2%) patients, with an overall response rate of 71%. Five (11%) patients had stable disease and 8 (18%) patients had progressive disease. At a median follow-up of 19.7 months, median time to progression for all patients was 19.9 months (95% confidence interval, 12.8 to 27 months). Median overall survival time was 28.4 months. Grade 3-4 nausea/vomiting and hematological toxicities were observed in 12 (26%) and 6 (13.3%) patients, respectively. Cardiac toxicity was observed in 2 (4.4%) patients. In this trial, paclitaxel and doxorubicin combination was demonstrated to be a favorable and active regimen in the first-line treatment of metastatic breast cancer.