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The Oncologist, Vol. 1, No. 4, 278–279, August 1996
© 1996 AlphaMed Press

SPECIAL SECTION
Correspondence

REGARDING: VALERO V, BUZDAR AU, HORTOBAGYI GN. "LOCALLY ADVANCED BREAST CANCER," THE ONCOLOGIST 1996;1:8-17.

Professor R.T.D. Oliver, M.D., F.R.C.P.1

1 Sir Maxwell Joseph Professor of Medical Oncology Colston Ward, First Floor, King George V Building St. Bartholomew’s Hospital West Smithfield, London EC1A 7BE United Kingdom

TO THE EDITORS: I read with interest Valero et al.’s review showing a lack of any increased cure rate over surgery from use of neoadjuvant combination therapy for locally advanced breast cancer, although a definite gain from breast conservation. Missing was any mention of hormone therapy [1] despite some of the best neoadjuvant results being from the use of Tamoxifen® in the elderly [2]. Interestingly, the highest complete remission rate in Valero et al.’s review (52%) was in a regimen including Tamoxifen® [3]. In addition, Bartlett et al. have reported that hormone therapy is superior to chemotherapy as adjuvant in estrogen receptor-positive tumors [4]. With new data from the study of radiotherapy demonstrating prostate tumor cell kill to be far higher when radiation treatment follows hormone therapy rather than when given concurrently or after therapy [5], there is a need for studies to investigate whether the same applies to hormone therapy when combined with chemotherapy in breast cancer.

Further support for this comes from the latest overview of the effect of menstrual cycle timing and breast cancer surgery. The greatest gain from operating on premenopausal women occurs when the operation takes place during the progestergenic phase of the menstrual cycle, particularly in advanced node-positive patients and those with high levels of progesterone pre-op attributed to high survival [6]. With increasing recognition that trauma-induced cytokine release can be a factor in tumor acceleration [7], there is a case to consider hormones followed by chemotherapy plus radiation before any major surgical interference [1], most particularly in the rare subgroup of poor-risk tumors arising during pregnancy [8].


   REFERENCES
Top
 References
References 
 

  1. Oliver RTD, Tobias JS, Gallagher CJ. Viewpoint - Prebiopsy neo-adjuvant therapy for breast cancer to prevent post surgery trauma-induced growth factor and immuno-suppression mediated tumour progression. Eur J Cancer 1996; 32a:396–397.
  2. Falk GL, Jones DG, Gray JG. Efficacy of Tamoxifen on the primary treatment of operable breast cancer in the high risk patient. Aust NZ J Surg 1989; 59:543–545.[Medline]
  3. Lippman ME, Sorace RA, Bagley CS et al. Treatment of locally advanced breast cancer using primary induction chemotherapy with hormonal synchronization followed by radiation therapy with or without debulking surgery. NCI Monogr 1986; 1:153–159.
  4. Bartlett K, Eremin O, Hutcheon A et al. Adjuvant ovarian ablation vs. CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Lancet 1993; 341:1293–1298.[Medline]
  5. Zietman AL, Prince EA, Nakfoor BM et al. Permanent tumour eradication by radiation is enhanced by prior androgen withdrawal in two experimental models. J Urol 1996;155:509a.
  6. Fentiman IS, Gregory WM. The hormonal milieu and prognosis in operable breast cancer. Cancer Surv 1993;18:149–163.[Medline]
  7. Oliver RTD. Does surgery disseminate or accelerate cancer? Lancet 1995;346:1506–1507.[Medline]
  8. Oliver RTD. Pregnancy and breast cancer. Lancet 1994;344:471–472.
 

AUTHORS’ RESPONSE

Vicente Valero, M.D., Assistant Professor of Medicine2, Aman U. Buzdar, M.D., Deputy Chairman2, Gabriel N. Hortobagyi, M.D., Department Chairman2

2 Department of Breast Medical Oncology The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston, TX 77030

We appreciate the comments of Professor Oliver regarding our review. It has been recognized for decades that breast cancer is a systemic disease. Regional and distant micro-metastases occur early, and are part of the natural history of this illness. Adjuvant chemotherapy is an integral part of the curative management of patients with primary breast cancer, including locally advanced breast cancer (LABC). The benefit derived from this therapeutic approach is well documented, and persists beyond 10 years of follow-up [1, 2]. While we recognize the paucity of studies in direct support of this statement in patients with operable LABC, a few randomized trials have been completed and published [3, 4], and the world overview of randomized trials also demonstrated this benefit [1, 2]. Several randomized studies are under way to assess the relative efficacy of primary (or neoadjuvant) versus adjuvant chemotherapy in patients with early breast cancer, as well as operable LABC. For patients with inoperable LABC the window of opportunity to perform randomized trials with local therapy only as a control arm was lost many years ago. However, the results of phase II trials compare favorably with outcomes of historical control series.

We agree that adjuvant hormonal therapy is also an integral part of optimal management of selected patients with LABC (those >50 years old, and with estrogen receptor-positive tumors). The world overview demonstrated an additive effect in women treated with both systemic modalities. Therefore, for this high-risk group of patients, combined hormone and chemotherapy for those who present with hormone-responsive breast cancer might be the treatment of choice. On the other hand, the role of neoadjuvant hormonal therapy alone remains to be defined. When we last reviewed this issue [5], only limited data were available, and the results did not appear superior to local treatments without systemic therapy. We (and others) are prospectively assessing the role of neoadjuvant tamoxifen in selected patients with LABC (those who are elderly and those patients unfit for chemotherapy). Professor Oliver’s comments about other important areas in breast cancer research were beyond the scope of our review.


   REFERENCES 
Top
 References
 References 
 

  1. Early Breast Cancer Trialists’ Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 1992;339:71–85.[Medline]
  2. Early Breast Cancer Trialists’ Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 1992;339:1–15.[Medline]
  3. Grohn P, Heinonen E, Klefstrom P et al. Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer. Cancer 1984;54:670–674.[Medline]
  4. Rivkin SE, Green S, Metch B et al. Adjuvant CMFVP versus melphalan for operable breast cancer with positive axillary nodes: 10-year results of a Southwest Oncology Group Study. J Clin Oncol 1989;7:1229–1238.[Abstract]
  5. Hortobagyi GN, Buzdar AU. Locally advanced breast cancer: a review including the MD Anderson experience. In: Ragaz J, Ariel IM, eds. High-Risk Breast Cancer. Berlin: Springer-Verlag, 1991:382-415.




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