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Does Neoadjuvant/Adjuvant Chemotherapy Change the Natural History of Classic Invasive Lobular Carcinoma?

Centro Paulista de Oncologia and Albert Einstein Hospital, São Paulo, Brazil

To the Editor:

In the January 1, 2005 issue of the Journal of Clinical Oncology, Cristofanilli et al¹ reported on a retrospective analysis of the role of primary chemotherapy in patients with invasive lobular carcinoma of the classic type (ILC). Based on the presented data, these patients tended to have a statistically significant higher stage and an increased chance of lymph node involvement at diagnosis, as well as a significant higher frequency of hormone-responsive disease and lower nuclear grade. These patients had significant lower rates of pathologic complete response (3% v 15%; P <.001) and a higher incidence of residual lymph node disease ( four positive lymph nodes, 41% v 26%; P =.001) after neoadjuvant chemotherapy and, based on our current knowledge, were expected to have had a much worse outcome.^2-4 However, as pointed out by the authors, the opposite has occurred. Chaturvedi et al have also recently reported similar data regarding the effectiveness of neoadjuvant chemotherapy in invasive lobular carcinoma.⁵ If we were to extrapolate these findings to the adjuvant setting, given the results of prospective randomized trials such as those published by Fisher et al and Mauriac et al,^6,7 we should worry about the actual effectiveness of adjuvant chemotherapy in ILC patients. However, at present, our studies of adjuvant and neoadjuvant chemotherapy do not take this histological distinction into account for stratification and/or treatment allocation. This might become a reason for potential methodological problems in those studies. More importantly, frequently used guidelines such as NCI,⁸ NCCN⁹ and the St. Gallen Consensus Conference,¹⁰ as well as prognostic tools such as Adjuvant!¹¹ still do not consider the potential differences in the natural history and treatment effectiveness between this ILC and invasive ductal carcinomas, potentially exposing ILC patients to ineffective treatment. Based on the results presented, it would seem that lobular carcinomas of the classic type and invasive ductal carcinomas are two very different pathologic entities, which should be studied and managed as such.

In fact it may be time for the oncology community to consider a prospective randomized trial to evaluate the role of adjuvant chemotherapy versus hormonal therapy in ILC patients.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCES

1. Cristofanilli M, Gonzalez-Angulo A, Sneige N, et al: Invasive lobular carcinoma classic type: Response to primary chemotherapy and survival outcomes. J Clin Oncol 23:41-48, 2005[Abstract/Free Full Text]

2. Thomas E, Holmes FA, Smith TL, et al: The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: Long-term results from a prospective randomized trial. J Clin Oncol 22:2294-2302, 2004[Abstract/Free Full Text]

3. Singh G, Binkley SM, Sneige N, et al: Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460-469, 1999[Abstract/Free Full Text]

4. McCready DR, Hortobagyi GN, Kau SW, et al: The prognostic significance of lymph node metastases after preoperative chemotherapy for locally advanced breast cancer. Arch Surg 124:21-25, 1989[Abstract/Free Full Text]

5. Chaturvedi S, Heys SD, Chaturvedi RS, et al: Primary chemotherapy for breast cancers. Does histological type of cancer matter? Breast Cancer Res Treat 88:S106, 2004 (suppl 1; abstr 2089)

6. Fisher B, Bryant J, Wolmark N, et al: Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672-2685, 1998[Abstract]

7. Mauriac L, MacGrogan G, Avril A, et al: Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: A unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS). Ann Oncol 10:47-52, 1999[Abstract/Free Full Text]

8. National Institutes of Health Consensus Development Panel. National Institutes of Health Consensus Development Conference Statement: Adjuvant Therapy for Breast Cancer, November 1-3, 2000. J Natl Cancer Inst Monogr 30:5-15, 2001

9. National Comprehensive Cancer Network (NCCN) guidelines for treatment of breast cancer, available online at http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf

10. Goldhirsch A, Wood WC, Gelber RC, et al: Meeting highlights: Updated international expert consensus on the primary therapy of early breast cancer. J Clin Oncol 21:3357-3365, 2003[Abstract/Free Full Text]

11. www.adjuvantonline.com

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Related Reply

• In Reply:
  Massimo Cristofanilli, AnaMaria Gonzalez-Angulo, and Gabriel Hortobagyi
  JCO 2005 23: 6796-6797 [Full Text]

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