Originally published as JCO Early Release 10.1200/JCO.2009.21.8271 on June 29 2009

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Reply to A. Balmanoukian et al

Department of Medical Oncology, Dubai Hospital, United Arab Emirates

Ana Maria Gonazalez-Angulo

Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Triple receptor–negative breast cancers, defined as the absence of estrogen, progesterone, and human epidermal growth factor receptors, account for approximately 15% of all breast cancers and is a major area of investigation because it is associated with a disproportionately high number of breast cancer deaths compared with other breast cancer subtypes. Several observational studies have also reported this subtype of breast cancer to occur with higher frequency among women of African American ethnicity, and thus is proposed as one factor contributing to the typically observed poor prognostic outcome of breast cancer in this cohort compared with women who are white.

Few studies have looked at differences in survival outcomes among women of different racial groups, all of whom have triple receptor–negative breast cancer. We previously reported on a cohort of 471 women with triple receptor–negative breast cancer diagnosed between 1996 and 2005 that were treated with preoperative chemotherapy and followed at the M. D. Anderson Cancer Center (Houston, TX).¹ Our results showed no significant differences in pathological complete response rates (pCR), 3-year recurrence-free survival, and overall survival between African American and white/other patients. In our multivariable model, no significant association was observed between race and recurrence-free (hazard ratio, 1.08; 95% CI, 0.69 to 1.68; P = .747) or overall (hazard ratio, 1.08; 95% CI, 0.69 to 1.68; P = .735) survival when patients who were classified as white/other were compared with African American patients. Based on the results obtained, we concluded that within the confines of the study cohort and retrospective design, pCR and survival outcomes were similar among women who are African American and those in the white/other category who had triple receptor–negative breast cancer and were treated with similar chemotherapy protocols at a single institute.

It is with keen interest that we read the results of the report by Balmanoukian et al,² whose study attempted to answer a similar question that we asked in our study: Are pCR rates and survival outcomes similar among women of different racial groups who have triple receptor–negative breast cancer? This time the cohort examined comes from Sidney Kimmel Comprehensive Cancer Center at John Hopkins (Baltimore, MD). Balmanoukian et al reported a cohort of 38 women with triple receptor–negative breast cancer who received preoperative chemotherapy. In this study, the authors reported significantly lower pCR and recurrence-free and overall survival rates among women who were African American compared with women categorized in the white/other group. Although they were not able to show significant differences between survival outcomes and race in their multivariable model, Balmanoukian et al reported that trends were observed that favored women who were in the white/other group compared with women who were African American.

The study by Balmanoukian et al² adds to the growing literature looking at survival differences in breast cancer among women of different racial groups. Although the study is similar to the one we reported earlier, there are a number of important differences that may make it difficult to compare results between the two. As rightly acknowledged by Balmanoukian et al, the cohort sample size in their study was significantly smaller than ours, making definitive conclusions difficult. In our cohort, more than 80% of women in both racial groups received an anthracyline and taxane combination; this information was not reported in the study by Balmanoukian et al. This omission is important, as a retrospective evaluation of the Cancer and Leukemia Group B 9344 study has reported a significant benefit to the addition of paclitaxel to doxorubicin and cyclophosamide in the subset of patients with triple receptor–negative disease. In our study, race was self-reported and as such we could not discern which patients were of true African American origin.¹ As such the group of African American patients in our study may not be directly comparable to the African American group reported by the Balmanoukian et al study. Lastly, Balmanoukian et al² did not report the components of their multivariable model, which would be important in order to judge the amount of residual confounding that may affect the final results.

Regardless of the differences between the two studies^1,2 the results we reported are supported at three levels. First, considering all other factors being equal, including factors such as accessibility to care and socioeconomic status, the question that arises is whether modern polychemotherapy regimens have the same efficacy among women with breast cancer who belong to different racial groups. Evidence indicates that the answer to this question is yes. Dignam³ reported on a study conducted to examine whether differences in outcomes existed among African American and white women with breast cancer who were enrolled in four separate National Surgical Adjuvant Breast and Bowel Project trials over a period of 20 years. Dignam showed similar disease-free survival when comparing African American women with white women for both lymph node–positive (RR, 1.04; 95% CI, 0.93 to 1.17) and –negative (RR, 1.06, 95% CI, 0.92 to 1.23) subgroups. Similarly, after excluding cases of death that were most likely not attributable to cancer, overall survival was similar between African Americans and whites. They concluded that African American and white women with breast cancer who present with similar stage and pathological characteristics appear to derive similar benefit from systemic chemotherapy within the confines of a clinical trial. Second, the question that arises now is whether the pharmacokinetics and pharmacodynamics of various chemotherapeutic agents used in the treatment of breast cancer is different among African American and white women. Although it would be impossible to go through an entire list of drugs commonly administered to women with breast cancer evidence from Cancer and Leukemia Group B 9871, the study indicates that docetaxel, a taxane frequently given to women with either metastatic or nonmetastatic breast cancer, has a similar pharmacokinetic and pharmacodynamic profile among African American and white women.⁴ Third, in order to prove a case that the differences in prognostic outcome observed between racial groups who have the same subtype of breast cancer is primarily due to biologic differences, a difference at the gene level would have to be demonstrated. The group at M. D. Anderson Cancer Center recently studied gene expression profiles of 98 triple receptor–negative breast cancer specimens, 19 of which belonged to African American women, 23 to Hispanic women, and 56 to white women.⁵ They reported no significant differences in pCR among the different racial groups and additionally were unable to demonstrate any differentially expressed genes among African American women compared with women in the other racial groups. Although the study is a small one and needs to be validated in an independent data set, the results suggest that at least among women with triple receptor–negative breast cancer, gene expression profiles among African American women are similar to that of women of other racial groups.

In conclusion, we believe we have presented a strong case to support the results of our study. However the results reported by Balmanoukian et al,² although based on a small cohort sample, serve to highlight the fact that results of single-institution retrospective studies need confirmation from larger multi-institutional prospective studies. Regardless of differences in survival outcomes between different racial groups, triple receptor–negative breast cancer remains a subtype associated with poorer prognostic outcome compared with other types of breast cancer. Future research will need to focus on comprehensively understanding this entity at the gene level and looking for specific molecular targets that will have a positive impact on altering its natural history and ultimately improving prognostic outcome across all racial groups.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Dawood S, Broglio K, Kau SW, et al: Triple receptor–negative breast cancer: The effect of race on response to primary systemic treatment and survival outcomes. J Clin Oncol 27:220–226, 2009.[Abstract/Free Full Text]

2. Balmanoukian A, Zhang A, Jeter S, et al: African American women who receive primary anthracycline- and taxane-based chemotherapy for triple receptor–negative breast cancer suffer worse outcomes compared with white women. J Clin Oncol 27:e35–e37, 2009.[Free Full Text]

3. Dignam JJ: Efficacy of systemic adjuvant therapy for breast cancer in African-American and White women. J Natl Cancer Inst Monogr 30:36–43, 2001 11773290.[Abstract/Free Full Text]

4. Lewis LD, Miller AA, Rosner GL, et al: A comparison of the pharmacokinetics and pharmacodynamics of docetaxel between African-American and White cancer patients: CALGB 9871. Clin Cancer Res 13:3302–3311, 2007 17545536.[Abstract/Free Full Text]

5. Dean-Colomb W, Yan K, Liedtke C, et al: Transcriptional profiles of triple receptor-negative breast cancer: Are White, Hispanic, and African-American women different? J Clin Oncol 26:750s; 2008 (suppl) abstr 22014.

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