This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mehta, R. S. Search for Related Content PubMed Articles by Mehta, R. S. Social Bookmarking                            What's this?

Hormone Receptor, Grade, Human Epidermal Growth Factor Receptor 2, and Topoisomerase II As Predictors of Response to Chemotherapy

Rita S. Mehta

Department of Internal Medicine/Division of Hematology Oncology, University of California, Irvine, Orange, CA

To the Editor:

Pritchard et al¹ report an interaction among human epidermal growth factor receptor 2 (HER-2) status and anthracycline and taxane chemosensitivity in their review, but they do not mention tumor grade. Multivariate analysis has revealed that Scarff-Bloom-Richardson grade 3 tumors respond better to neoadjuvant treatment than Scarff-Bloom-Richardson grade 1 tumors (P < .0001).² A recent study suggests that an interaction between HER-2 and estrogen-receptor pathways may lead to a higher proliferation rate and thus a higher tumor grade.³ Therefore, inclusion of tumor grade in all the reviewed trials would have provided the relative predictive value of HER-2 status and grade in predicting anthracycline and taxane chemosensitivity.³ Moreover, among patients who have HER-2–negative, estrogen receptor–positive and or progesterone receptor–positive breast cancer, those with higher tumor grades may benefit from anthracycline and taxanes.² Furthermore, patients who have HER-2–negative, estrogen receptor–negative, and progesterone receptor–negative breast cancer, there is a high rate of pathologic complete response, specifically with anthracyclines administered biweekly compared with every 3 weeks, and paclitaxel administered weekly compared with every 3 weeks, and thus improved survival.^4-6 Of the prospectively maintained database of 14 patients with stage II-III or local relapse HER-2–negative, estrogen receptor–negative, and progesterone receptor–negative infiltrating ductal carcinoma of breast who received dose-dense doxorubicin and cyclophosphamide followed by either dose-dense paclitaxel (n = 2) or once-a-week paclitaxel (cremophor- or albumin-bound) with carboplatin (both 3 weeks on, 1 week off; n = 12) plus or minus six doses of bevacizumab every 2 weeks (n = 4), 10 (71%; 95% CI, 42% to 92%) of 14 patients achieved pathologic complete response. The progression-free survival of 86% of 14 patients at a median follow-up of 33 months is promising. Therefore, the high pathologic complete response reported by us parallels the benefit of biweekly anthracyclines, and biweekly or weekly paclitaxel scheduling in phase III trials.^4,5 In an otherwise comprehensive review by Pritchard et al, it needs to be emphasized that within patients with HER-2–negative tumors, patients with estrogen receptor–negative and progesterone receptor–negative subtype (triple-negative), or patients with higher tumor grade, optimally scheduled doxorubicin and cyclophosphamide and paclitaxel should be standard.^4,5 The potential additional benefit of carboplatin and bevacizumab over optimum scheduling of standard chemotherapy needs to be tested in randomized trials.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: None Honoraria: Rita S. Mehta, ABRAXIS Oncology Research Funding: None Expert Testimony: None Other Remuneration: None

NOTES

published online ahead of print at www.jco.org on April 28, 2008

REFERENCES

1. Pritchard KI, Messersmith H, Elavathil L, et al: HER-2 and Topoisomerase II as predictors of response to chemotherapy. J Clin Oncol 26:736-744, 2008[Abstract/Free Full Text]

2. Amat S, Penault-Llorca F, Cure H, et al: Scarff-Bloom-Richardson (SBR) grading: A pleiotropic marker of chemosensitivity in invasive ductal breast carcinomas treated by neoadjuvant chemotherapy. Int J Oncol 20:791-796, 2002[Medline]

3. Bartlett JMS, Ellis IO, Dowsett M, et al: Human epidermal growth factor receptor 2 status correlates with lymph node involvement in patients with estrogen receptor (ER) negative, but with grade in those with ER-positive early-stage breast cancer suitable for cytotoxic chemotherapy. J Clin Oncol 25:4423-4430, 2007[Abstract/Free Full Text]

4. Berry DA, Cirrincione C, Henderson IC, et al: Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295:1658-1667, 2006 [Erratum: JAMA 295:2356, 2006][Abstract/Free Full Text]

5. Sparano JA, Wang M, Martino S, et al: Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 358:1663-1671, 2008[Abstract/Free Full Text]

6. Chen JH, Mehta RS, Carpenter PM, et al: Magnetic resonance imaging in predicting pathological response of triple negative breast cancer following neoadjuvant chemotherapy. J Clin Oncol 25:5667, 2007[Free Full Text]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				R. S. Mehta, D. Jackson, and T. Schubbert Metronomic Schedule of Paclitaxel Is Effective in Hormone Receptor-Positive and Hormone Receptor-Negative Breast Cancer J. Clin. Oncol., June 20, 2009; 27(18): 3067 - 3068. [Full Text] [PDF]

				R. S. Mehta Dose-Dense and/or Metronomic Schedules of Specific Chemotherapies Consolidate the Chemosensitivity of Triple-Negative Breast Cancer: A Step Toward Reversing Triple-Negative Paradox J. Clin. Oncol., July 1, 2008; 26(19): 3286 - 3288. [Full Text] [PDF]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mehta, R. S. Search for Related Content PubMed Articles by Mehta, R. S. Social Bookmarking                            What's this?