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 Google Scholar Google Scholar Articles by Nguyen, P. L. Articles by Harris, J. R. Search for Related Content PubMed Articles by Nguyen, P. L. Articles by Harris, J. R. Social Bookmarking                            What's this?

In Reply

Harvard Radiation Oncology Program, Boston, MA

Alphonse G. Taghian

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA

Jay R. Harris

Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA

We are grateful to Drs Roukos, Lykoudis, and Liakakos for their thoughtful commentary and discussion about what our data adds to the overall goal of identifying women with breast cancer who are at highest risk for local recurrence.¹ Earlier this year in Journal of Clinical Oncology, Kyndi et al² also noted our observation of increased local recurrence for the human epidermal growth receptor 2 (HER-2) subtype (estrogen receptor [ER] –negative/progesterone receptor [PR] –negative/HER-2–positive) and basal subtype (ER-negative/PR-negative/HER-2-negative) after breast-conserving therapy (BCT) in patients undergoing mastectomy. In the subgroup of 1,000 women who underwent mastectomy with or without radiation therapy as part of the Danish 82b/c randomized trials and had tissue available for ER/PR/HER-2 evaluation, Kyndi et al similarly reported that both the HER-2 and basal subtypes were significantly associated, on multivariable analysis, with an increased risk of locoregional recurrence compared with luminal subtypes. Given that none of the HER-2–positive patients in either our series or the Danish study received trastuzumab, these findings are most clinically relevant for the basal subtype, in whom there are currently still no targeted therapies.

Given the increased risk of local recurrence among patients with the basal subtype compared with luminal subtypes, Roukos et al raise the possibility that these women might benefit from more aggressive surgery. But given that patients with the basal subtype have higher local recurrence in both the BCT and mastectomy settings, we agree with their assessment that there currently are not enough data to mandate such an approach. For patients with the basal subtype who also have BRCA1 mutations, we generally consider bilateral mastectomy as the preferred treatment due to the substantial risk of second primary tumors arising in either the ipsilateral or contralateral breast in these patients.^3,4 For patients with basal tumors who do not have a BRCA1 mutation, we are unaware of any data suggesting an increased risk of second primary cancers. Additional studies of strategies are needed to improve local control for the basal subtype, possibly including more extensive surgery, increased radiation boost, novel use of chemoradiotherapy or other approaches at radiosensitization.

Drs Roukos, Lykoudis, and Liakakos also mention that our findings of the ER-positive patients may be less clinically relevant now due to the improved outcomes that might be expected from more widespread use of aromatase inhibitors, but given the low 5-year rates of local recurrence seen in the luminal A (0.8%) and luminal B (1.5%) groups, we feel these findings would be unlikely to change substantially with increased aromatase inhibitor use. However, it is appropriate to be cautious about 5-year results, given that luminal breast cancers can recur well beyond 5 years, whereas nonluminal types tend to fail early, and therefore longer follow-up will be needed to confirm these findings.^5,6

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

ACKNOWLEDGMENTS

Supported in part by the NCI/AVON supplement to NCI SPORE award, P50 CA89393, entitled, "Dana-Farber SPORE in Breast Cancer," and in part by the Jane Mailloux Fund, the Blanche Montesi Fund, and the Tim Levy Fund for breast cancer research (A.G.T.).

REFERENCES

1. Nguyen PL, Taghian AG, Katz MS, et al: Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 26:2373-2378, 2008[Abstract/Free Full Text]

2. Kyndi M, Sorensen FB, Knudsen H, et al: Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: The Danish Breast Cancer Cooperative Group. J Clin Oncol 26:1419-1426, 2008[Abstract/Free Full Text]

3. Pierce LJ, Levin AM, Rebbeck TR, et al: Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 24:2437-2443, 2006[Abstract/Free Full Text]

4. Veronesi A, de Giacomi C, Magri MD, et al: Familial breast cancer: Characteristics and outcome of BRCA 1-2 positive and negative cases. BMC Cancer 5:70, 2005[CrossRef][Medline]

5. Anderson WF, Chen BE, Jatoi I, et al: Effects of estrogen receptor expression and histopathology on annual hazard rates of death from breast cancer. Breast Cancer Res Treat 100:121-126, 2006[CrossRef][Medline]

6. Hess KR, Pusztai L, Buzdar AU, et al: Estrogen receptors and distinct patterns of breast cancer relapse. Breast Cancer Res Treat 78:105-118, 2003[CrossRef][Medline]

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

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 Google Scholar Google Scholar Articles by Nguyen, P. L. Articles by Harris, J. R. Search for Related Content PubMed Articles by Nguyen, P. L. Articles by Harris, J. R. Social Bookmarking                            What's this?