Pilot Study on Adjuvant Chemotherapy and Hormonal Therapy for Irradiated Inoperable Breast Cancer

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m2 as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m2 every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

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Primary tumor and patient characteristics in breast cancer as predictors of adjuvant chemotherapy regimen: A regression model

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e11632 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e11632-e11632

Author(s):

V. Francescutti ◽

F. Farrokhyar ◽

R. Tozer ◽

B. Heller ◽

P. Lovrics ◽

...

Keyword(s):

Breast Cancer ◽

Logistic Regression ◽

Adjuvant Chemotherapy ◽

Regression Model ◽

Hormonal Therapy ◽

Chemotherapy Regimen ◽

Univariate Analysis ◽

Stepwise Logistic Regression ◽

Adjuvant Radiation ◽

Tumor Characteristics

e11632 Background: Adjuvant chemotherapy is used to reduce the risk of recurrence of breast cancer. This study was undertaken to determine which patient and tumor characteristics are important in guiding the choice of adjuvant chemotherapy. Methods: A retrospective review was undertaken of patients diagnosed with breast cancer (stages I-III) at a regional cancer center from 2004–7. Patient and tumor characteristics were identified and chemotherapy regimens compared. Binary logistic regression analysis was performed to the choice of FEC/D, CEF, AC/T, or ddAC/T against AC or CMF, or the choice of chemotherapy to hormonal therapy only. Univariate analysis was used to select factors (p<0.1) for entry into a multivariate stepwise logistic regression model using the forward method. Odds ratios with 95% CI were calculated. A p-value of < 0.05 was significant and comparisons were two tailed. Results: Model 1 (n=871) included regimen (AC or CMF vs. aggressive regimen) as the dependant variable. Indicators of choice of aggressive regimen were higher stage [OR 4.7 (CI 3.3, 6.8)], positive nodes [2.5 (1.6, 3.8)], negative PR [2.1 (1.4, 3.1)], higher grade [1.4 (1.0, 1.8)], and age [0.91 (0.88, 0.92)]. Model 2 (n=640) involved choice of any regimen (chemotherapy vs. hormonal therapy only) as the dependant variable. Indicators of choice of chemotherapy were higher stage [7.19 (2.8, 18.4)], higher grade [7.02 (3.3, 14.8)], positive nodes [3.25 (0.98, 10.77)], age [0.85 (0.81, 0.90)], and ER negativity [0.04 (0.004, 0.37)]. Factors not significant in both models were: family history, comorbidities (renal/hepatic dysfunction, diabetes, cardiac history, or neuropathy), treating medical oncologist, histology, Her2/neu, > 3 positive nodes, ratio of positive to total nodes, multicentricity, multifocality, and positive margin status. Conclusions: This study verifies known important factors for choice of chemotherapy regimen as found in current guidelines, quantifies their effects at our center, and excludes others thought to be important. Further studies are required to confirm these results both nationally and internationally, where risk stratification may be different, and if variables predicting adjuvant radiation therapy are similar. No significant financial relationships to disclose.

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Breast Cancer Treatment Guidelines in Older Women

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.175 ◽

2005 ◽

Vol 23 (4) ◽

pp. 783-791 ◽

Cited By ~ 165

Author(s):

Sharon H. Giordano ◽

Gabriel N. Hortobagyi ◽

Shu-Wan C. Kau ◽

Richard L. Theriault ◽

Melissa L. Bondy

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Adjuvant Chemotherapy ◽

Older Women ◽

Surgical Therapy ◽

Hormonal Therapy ◽

Treatment Guidelines ◽

Clinical Stage ◽

Adjuvant Hormonal Therapy ◽

Comorbidity Score

Purpose To determine patterns and predictors of concordance with institutional treatment guidelines among older women with breast cancer. Methods The study population included 1,568 patients aged 55 years and older who were treated at M.D. Anderson Cancer Center between July 1997 and January 2002 for stage I to IIIA invasive ductal and lobular breast cancer. Concordance with institutional guidelines was determined for definitive surgical therapy, radiotherapy after breast-conserving surgery, radiation therapy after mastectomy, adjuvant chemotherapy use, and adjuvant hormonal therapy use. The following variables were considered as possible modifiers of concordance: patient age, marital status, race, educational level, Eastern Cooperative Oncology Group performance status, comorbidity score, clinical stage, hormone receptor status, HER2-neu status, tumor grade, pathologic tumor size, lymphatic invasion, and number of lymph nodes involved. Logistic regression modeling was performed to determine the independent effect of each variable on guideline concordance. Results Older women were less likely to receive treatment in concordance with guidelines for definitive surgical therapy (P < .001), postlumpectomy radiation (P = .03), adjuvant chemotherapy (P < .001), and adjuvant hormonal therapy (P < .001). In multivariate analysis, age ≥ 75 years predicted a deviation from guidelines for definitive surgical therapy, adjuvant chemotherapy, and adjuvant hormonal therapy. Nonwhite race was associated with decreased likelihood of adjuvant radiation therapy after breast conservation. Conclusion After adjustment for comorbidity score, race, marital status, educational status, clinical stage, and tumor characteristics, increasing patient age was independently associated with decreased guideline concordance for definitive surgery, adjuvant chemotherapy, and adjuvant hormonal therapy. Future research should focus on delineating the possible reasons for guideline discordance.

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Adjuvant Chemotherapy with a Combination of Mitoxantrone, Methotrexate, 5-Fluorouracil for Node-Positive Breast Cancer: Phase II Pilot Study

Journal of Chemotherapy ◽

10.1179/joc.1999.11.5.396 ◽

1999 ◽

Vol 11 (5) ◽

pp. 396-401 ◽

Cited By ~ 1

Author(s):

M. Kanno ◽

S. Nakamura ◽

C. Uotani ◽

T. Taniya ◽

T. Mura ◽

...

Keyword(s):

Breast Cancer ◽

Pilot Study ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Node Positive ◽

Positive Breast Cancer

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P104 Adjuvant chemotherapy plus alternated hormonal therapy (AVCF-TM) for HR+ N+ breast cancer: 13-year results of a randomized phase III trial

European Journal of Cancer ◽

10.1016/s0959-8049(97)89321-5 ◽

1998 ◽

Vol 34 ◽

pp. S40-S41

Author(s):

M. Di Palma ◽

S. Delaloge ◽

S. Guérin ◽

P. Fargeot ◽

T. Conroy ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Hormonal Therapy ◽

Phase Iii ◽

Phase Iii Trial

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Offering a choice between two adjuvant chemotherapy regimens: a pilot study to develop a decision aid for women with breast cancer

Patient Education and Counseling ◽

10.1016/s0738-3991(98)00117-7 ◽

1999 ◽

Vol 37 (3) ◽

pp. 283-291 ◽

Cited By ~ 20

Author(s):

Ellen Irwin ◽

Andrew Arnold ◽

Timothy J. Whelan ◽

Leonard M. Reyno ◽

Patricia Cranton

Keyword(s):

Breast Cancer ◽

Pilot Study ◽

Adjuvant Chemotherapy ◽

Decision Aid

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The 70-gene profile and chemotherapy benefit in 1,600 breast cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.512 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 512-512 ◽

Cited By ~ 2

Author(s):

R. A. Bender ◽

M. Knauer ◽

E. J. Rutgers ◽

A. M. Glas ◽

F. A. de Snoo ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Endocrine Therapy ◽

Hormonal Therapy ◽

Prognostic Indicator ◽

Low Risk ◽

Breast Cancer Patients ◽

Node Negative

512 Background: The 70-gene expression profile (MammaPrint) is validated as an independent prognostic indicator for breast cancer patients with T1–2 node-negative and positive disease regardless of estrogen receptor status. Here we present the relationship between MammaPrint outcome and chemotherapy benefit in the adjuvant setting. Methods: We performed a pooled analysis of 1,637 patients with MammaPrint outcomes (T1–2, node-negative and positive invasive breast cancer and median FU 7.1 yrs) to determine the chemotherapy benefit of patients treated with adjuvant chemotherapy in addition to endocrine therapy. Patients were collected from 7 large datasets at multiple institutions across Europe. Results: In this meta-analysis, MammaPrint assigned 772 patients (47%) to “low risk” and 865 (53%) to “high risk”. In total 349 patients were treated with endocrine therapy alone, whereas 226 were treated with both chemo- and endocrine therapy. Patients with poor prognosis MammaPrint profile had a substantial benefit from chemotherapy: At 5 years, distant disease-free survival was improved from 69% to 88% (HR 0.28 (95% CI 0.14–0.56, p<0.001) when chemotherapy was added to hormonal therapy. The results remained significant in multivariate analysis including stratification by standard clinico-pathologic prognostic factors. Patients classified by MammaPrint as good prognosis (“low risk”) had no significant benefit from chemotherapy (p=0.962). Conclusions: The 70-gene MammaPrint profile is not only a strong and independent prognostic indicator for patients with early stage breast cancer, but it may also be predictive for the benefit of chemotherapy. While MammaPrint “high risk” classified patients demonstrate a clear benefit from adjuvant chemotherapy added to hormonal therapy, patients classified by MammaPrint as “low risk” for recurrence do not appear to benefit from the addition of chemotherapy to hormonal treatment alone. [Table: see text]

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