Local Therapy in BRCA1/2 Carriers with Operable Breast Cancer: Comparison of Breast Conservation and Mastectomy.

PURPOSE: To investigate the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response of primary operable breast cancer. PATIENTS AND METHODS: Patients (tumor size ≥ 3 cm, N0 to 2, M0) were prospectively randomized to receive every 14 days a total of four cycles of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2, either with (ADocT) or without (ADoc) simultaneous tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment. RESULTS: Within 14 months, 250 patients were included in the study at 56 centers. Of 992 planned cycles, 97.9% were administered. Pathologically complete remission (pCR) with no detectable viable tumor cells was achieved in 9.7%. There was a nonsignificant difference of −1.2% in favor of ADoc, with a 95% confidence interval of −8.6% to 6.2%. A further 2.4% had only noninvasive tumor residues, and 13.8% had focal invasive residues. Complete and partial responses detected by palpation were observed in 28.9% and 52.4%, respectively. The response rates (complete and partial) by best appropriate imaging methods were 77.5% and 67.5% for ADocT and ADoc, respectively. Breast conservation was possible in 68.8% of the patients. A tendency toward more frequent toxic events was observed with ADocT treatment. Significant predictors of pCR to chemotherapy were negative lymph node and negative estrogen receptor status. CONCLUSION: A dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and rapid efficacy as a form of preoperative chemotherapy in operable breast cancer. Concurrent treatment with tamoxifen for 8 weeks could not improve the pathologic response rate.

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7N Local therapy options in BRCA1/2 carriers with operable breast cancer: the importance of adjuvant chemotherapy

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(10)70034-3 ◽

2010 ◽

Vol 8 (3) ◽

pp. 55 ◽

Cited By ~ 1

Author(s):

L. Pierce ◽

K. Phillips ◽

K. Griffith ◽

S. Buys ◽

D. Gaffney ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Local Therapy ◽

Operable Breast Cancer ◽

Therapy Options

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A comparative study of post-operative psychosocial function in women with primary operable breast cancer randomized to breast conservation therapy or mastectomy

European Journal of Surgical Oncology ◽

10.1016/s0748-7983(97)90804-0 ◽

1997 ◽

Vol 23 (4) ◽

pp. 327-334 ◽

Cited By ~ 55

Author(s):

B. Poulsen ◽

H.P. Graversen ◽

J. Beckmann ◽

M. Blichert-Toft

Keyword(s):

Breast Cancer ◽

Comparative Study ◽

Breast Conservation ◽

Breast Conservation Therapy ◽

Operable Breast Cancer ◽

Psychosocial Function ◽

Primary Operable Breast Cancer

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Preoperative Therapy in Invasive Breast Cancer: Pathologic Assessment and Systemic Therapy Issues in Operable Disease

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.3510 ◽

2008 ◽

Vol 26 (5) ◽

pp. 814-819 ◽

Cited By ~ 246

Author(s):

Julie R. Gralow ◽

Harold J. Burstein ◽

William Wood ◽

Gabriel N. Hortobagyi ◽

Luca Gianni ◽

...

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Systemic Therapy ◽

Cancer Biology ◽

Tumor Response ◽

Breast Conservation ◽

Operable Breast Cancer ◽

Preoperative Therapy ◽

Pathologic Assessment ◽

State Of The Science

PurposeTo review the state of the science with respect to preoperative systemic therapy and pathologic assessment in operable breast cancer.MethodsThis article reviews data presented at the National Cancer Institute State of the Science Conference on Preoperative Therapy in Invasive Breast Cancer as well as supporting published data.ResultsPreoperative chemotherapy in operable breast cancer has been shown to improve breast conservation rates as a result of tumor response to therapy. When patients are given preoperative systemic therapy, regimens should be the same as those established as safe and active in the adjuvant setting. At present, there are no data to suggest that systemic treatment should be tailored based on initial tumor response, or based on the extent of residual disease. In operable breast cancer, there seems to be no survival advantage from initiation of systemic therapy before surgery. A variety of clinical, imaging, and pathologic measurements are available to gauge tumor response to treatment. There is a clear correlation between tumor response in the breast and lymph nodes and both disease-free and overall survival. Pathologic complete response and other pathologic measures may be useful as surrogate end points in evaluating and understanding new therapies.ConclusionIn operable breast cancer, preoperative systemic therapy is effective and can improve breast conservation rates. Unless the tumor is large or the patient is in a clinical trial, postoperative adjuvant systemic therapy is the standard of care. To achieve optimal outcomes, preoperative systemic therapy must be administered as part of a coordinated, multimodality treatment program. The preoperative setting provides a unique opportunity to study the impact of systemic therapies on breast cancer biology.

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Doxorubicin With Cyclophosphamide Followed by Docetaxel Every 21 Days Compared With Doxorubicin and Docetaxel Every 14 Days As Preoperative Treatment in Operable Breast Cancer: The GEPARDUO Study of the German Breast Group

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.078 ◽

2005 ◽

Vol 23 (12) ◽

pp. 2676-2685 ◽

Cited By ~ 286

Author(s):

Gunter von Minckwitz ◽

Günter Raab ◽

Angelika Caputo ◽

Martin Schütte ◽

Jörn Hilfrich ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Breast Conservation ◽

Sequential Therapy ◽

Operable Breast Cancer ◽

Phase Iii ◽

Clinical Response Rate ◽

Preoperative Treatment ◽

Sequential Administration ◽

Dose Dense

Purpose Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer. Methods This phase III study investigated 913 women with untreated operable breast cancer (T2-3, N0-2, M0) randomly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with filgrastim support (ADOC), or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each (AC-DOC). The primary end point was the incidence of pathologic complete (invasive and noninvasive) response (pCR) in the breast and axillary nodes. Secondary end points were predictors for pCR, clinical response, rate of breast conservation, and safety. Results A pCR was achieved in 94 patients (10.6%), but the likelihood was significantly greater with AC-DOC (14.3%; n = 63) than with ADOC (7.0%; n = 31) (odds ratio, 2.22; 90% CI, 1.52 to 3.24; P < .001). Independent predictors of attaining a pCR included the use of sequential therapy, high tumor grade, and negative hormone receptor status. The response rates detected by palpation and by imaging were significantly higher with AC-DOC (85.0% and 78.6%, respectively) than with ADOC (75.2% and 68.6%, respectively; both P values < .001). The rate of breast-conserving surgery was 63.4% for AC-DOC and 58.1% for ADOC (P = .05). Predominant grade 3/4 toxicities were leucopenia (AC-DOC, 74.2%; ADOC, 53.7%) and neutropenia (AC-DOC, 66.4%; ADOC, 44.7%) but were infrequently associated with fever (AC-DOC, 4.6%; ADOC, 3.1%). Conclusion Sequential AC-DOC is more effective at inducing pCR than dose-dense ADOC as preoperative treatment for patients with operable breast cancer.

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Clinical prognostic and predictive factors for primary chemotherapy in operable breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.1.107 ◽

1998 ◽

Vol 16 (1) ◽

pp. 107-114 ◽

Cited By ~ 83

Author(s):

P Ellis ◽

I Smith ◽

S Ashley ◽

G Walsh ◽

S Ebbs ◽

...

Keyword(s):

Breast Cancer ◽

Local Recurrence ◽

Prognostic Significance ◽

Breast Conservation ◽

Disease Free Survival ◽

Axillary Node ◽

Operable Breast Cancer ◽

Primary Chemotherapy ◽

Free Survival ◽

Node Status

PURPOSE This study aimed to identify clinical factors that are of prognostic significance or that predict for subsequent treatment outcome in patients with large operable breast cancer treated with primary chemotherapy (PCT) at our institution. METHODS One hundred eighty-five patients received the following regimens: CMF or MMM (76 patients), ECF (75 patients), AC or FEC (34 patients), followed by surgery, with radiotherapy (RT) given to those with breast conservation. A number of common clinical variables were assessed in relation to local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). RESULTS Clinical responders had improved DFS (P = .009) and OS (P = .08) compared with nonresponders. There was no association between clinical or pathologic complete remission (CR) and survival. Pretreatment clinical axillary node positivity was a significant predictor of worsened DFS (P = .0001), OS (P = .0001), and LRFS (P = .03). Patients remaining clinically node-positive postchemotherapy had an inferior outcome compared with those becoming node-negative (DFS, P = .03; OS, P = .03) but pathologic axillary node status was not shown to predict for survival. Twenty-nine patients in clinical CR following PCT who electively did not have surgery and were treated with RT alone had significantly increased local recurrence rate compared with partial responders having surgery and RT (P = .02). There were no differences in DFS or OS between these groups. On multivariate analysis, clinical axillary node status was the only independent predictor of OS and DFS, and LRFS. CONCLUSION Pretreatment and posttreatment clinical axillary node status is a major predictor of outcome following PCT. Complete clinical response does not define a more favorable subgroup compared with those not obtaining CR.

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