Electronic letters to:

Review:
Tamara Shenkier, Lorna Weir, Mark Levine, Ivo Olivotto, Timothy Whelan, and Leonard Reyno
Clinical practice guidelines for the care and treatment of breast cancer: 15. Treatment for women with stage III or locally advanced breast cancer
CMAJ 2004; 170: 983-994 [Abstract] [Full text] [PDF]
*eLetters: Submit a response to this article

Electronic letters published:

[Read eLetter] The role taxanes in Stage III or locally advanced breast cancer
deepu mirchandani   (2 April 2004)
[Read eLetter] IIIC - A Problematic New Breast Cancer Stage
Joseph L Pater   (26 March 2004)
[Read eLetter] The need for comprehensive care of patients with locally advanced breast cancer.
Sunil Verma   (24 March 2004)

The role taxanes in Stage III or locally advanced breast cancer 2 April 2004
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deepu mirchandani
saskatoon cancer center

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Re: The role taxanes in Stage III or locally advanced breast cancer

dmirchandani{at}scf.sk.ca deepu mirchandani

We concur with Verma et al.[1] on the importance of neoadjuvant sequential anthracycline and taxotere administration in a near doubling of complete pathologic response [pCR] and in improving overall survival by 15% [P-value 0.04] over a similar number of cycles of anthracyclines[2].

Furthermore, in the adjuvant therapy of the operable patient with node-positive breast cancer, cross-trial comparison over similar follow-up periods indicate that AC for 4 cycles followed by taxol for 4 cycles [3,4] has a lower incidence of acute leukemia than regimes with six cycles of anthracyclines and alkylating agents [5,6]. Even as AC followed by taxol is compared to CEF within the randomized Phase III MA.21 trial, the above side-effect profile should not be ignored when discussing adjuvant chemotherapy.

In summary, for neoadjuvant therapy, the sequential use of anthracyclines followed by taxotere offers an increase in pCR and in overall survival over use of anthracylines alone. Moreover the adjuvant use of taxanes offers an opportunity to move away from the increase in acute leukemia associated with the use of more anthracyclines and alkylators. With these data, the use of taxanes in the above situations requires inclusion in clinical guideline development.

Deepu Mirchandani, Kamal Haider, Haji Chalchal, Shahid Ahmed, Mohammed Salim: Saskatoon Cancer Center, and Allan Blair Cancer Center

REFERENCES:

1. Verma S, Clemons M, Fitzgerald B, Freedman O. The need for comprehensive care of patients with locally advanced breast cancer. CMAJ Mar 24 2004, 170: 983
2. Hutcheon AW, Heys SD, Sarkar TK, Ogston KN, Eremin O, Walker LG, Miller ID. Docetaxel primary chemotherapy in breast cancer: a five-year update of the Aberdeen trial. Abstract 11; SABCS Dec 2003.
3. Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer . J Clin Oncol 21(6) 2003: 976-983.
4. Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, et al. Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol (21) 8, 2003:1431-1439.
5. Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H et al. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group J Clin Oncol, (16) 2651-2658, 1998.
6. Piccart MJ, Leo AJ, Beauduin M, Vindevoghel A, Michel J, Focan C. et al. Phase III Trial Comparing Two Dose Levels of Epirubicin Combined With Cyclophosphamide With Cyclophosphamide, Methotrexate, and Fluorouracil in Node-Positive Breast Cancer . J Clin Oncol (19) 12, 2001: 3103-3110.

Conflict of Interest:

None declared
IIIC - A Problematic New Breast Cancer Stage 26 March 2004
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Joseph L Pater
Queen's University

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Re: IIIC - A Problematic New Breast Cancer Stage

jpater{at}ctg.queensu.ca Joseph L Pater

In their article on guidelines for managing locally advanced breast cancer, Shenkier et al.1 mention the difficulty they faced in dealing with the changes introduced in the 2002 TNM tumour-staging system. Their comment needs amplification, I think, because, if anything, it understates the potential confusion caused by the introduction of a new category, Stage IIIC.

Stage IIIC is defined as including patients with any T category and pN3 disease. PN3 in turn has three subcategories, the third (pN3c) of which, supraclavicular node involvement, is the focus of Shenkier et al’s comments. As they state, there is now some evidence to support treating these patients as having inoperable locally advanced, rather than metastatic, disease. However, pN3a and pN3b indicate types of nodal involvement (>10 axillary, infraclavicular and internal mammary) that have little or nothing to do with operability. Most such patients would be managed in the manner Shenkier et al describe for operable Stage IIIA disease.

It is unfortunate that the newly introduced Stage IIIC category includes two groups of patients for whom management strategies are quite different. Indeed, its utility as a descriptive category has to be questioned, particularly in the context of management guidelines. In this setting it might have been better to use specific T and N categories, since the guideline as published appears to imply that Stage IIIC is simply equivalent to supraclavicular node involvement.

1 Shenkier T, Weir L, Levine M, Olivotto I, Whelan T, Reyno L. Clinical practice guidelines for the care and treatment of breast cancer: 15. Treatment for women with stage III or locally advanced breast cancer. CMAJ 2004;170(6):983-94

Conflict of Interest:

None declared
The need for comprehensive care of patients with locally advanced breast cancer. 24 March 2004
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Sunil Verma
Toronto Sunnybrook Regional Cancer Centre

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Re: The need for comprehensive care of patients with locally advanced breast cancer.

sunil.verma{at}sw.ca Sunil Verma

The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer recently presented an important and thorough overview of the treatment of women with locally advanced breast cancer (LABC).(1) We would like to add a few points to their analysis:

1. LABC compromises a heterogeneous group of breast tumors, which may include neglected indolent cancers, inoperable cancers, or rapidly growing inflammatory breast cancers. The natural history of this group as a whole is therefore very difficult to characterize. Due to the importance of combined-modality therapy and the specialized and complicated needs of these patients, we now have a specific clinic dedicated to the treatment of women with LABC at the Toronto-Sunnybrook Regional Cancer Centre. This clinic is led by an Advanced Practice Nurse, and is the first and largest of its kind in Canada that we are aware of. This interdisciplinary professional practice model is focused on coordinated treatment planning among the various disciplines and is an appropriate delivery model in today's health care environment.(2) This approach is integral to treating the unique needs of these patients, and will contribute to our understanding of this complex illness.

2. In their practice guidelines, only the role of chemotherapy in the neoadjuvant setting was discussed. Currently, neoadjuvant hormonal therapy with third generation aromatase inhibitors (AI) is gaining importance in this population, especially in elderly, postmenopausal woman whose breast cancer is ER and/or PR positive. The importance of neoadjuvant hormone therapy with AIs and their superiority over tamoxifen in this setting has been demonstrated in two randomized trials. (3,4)

3. The authors discuss the evolving role of AIs in the adjuvant setting (5) other recent studies have shown the benefit of AIs after tamoxifen.(6,7) The rapidly accumulating evidence in favour of AIs necessitates frequent updating of guidelines with respect to adjuvant hormonal therapy.

4. Taxane therapy should now be considered standard of care. The authors include the results of two large trials - Aberdeen and NSABP-B27, which clearly show an substantial improvement in the pathologic response achieved in patients receiving taxanes in addition to anthracyclines.(8,9) Recent presentation of longer follow-up from the Aberdeen group also supports growing evidence of improvement in survival with the addition of taxane chemotherapy. (10)

We would again like to congratulate the authors of this review on writing on this very important subject.

Sincerely,

Dr. Sunil Verma MD, FRCP(C)

Dr. Mark Clemons MD, MRCP

Barbara Fitzgerald RN, MSN

Dr. Orit Freedman MD

Toronto Sunnybrook Regional Cancer Centre 2075 Bayview Avenue, Toronto, ON. M4N 3M5

References

1. Shenkier T, Weir L, Levine M, Olivetto I, Whelan T, and L Reyno for the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Clinical Practice Guidelines for the care and treatment of breast cancer:15. Treatment for women with stage III or locally advanced breast cancer. CMAJ 2004 170 (6), 983-993.

2. O'Rourke, M.W. Rebuilding a professional practice model. The return of role-based practice accountability. Nursing Administration Quarterly 2003, 27(2), 95-105.

3. Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Janicke F et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1 and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: Evidence from a phase III randomized trial. JCO 2001, 19(18), 3808-3816.

4. Smith I, Dowsett M, on behalf of the IMPACT Trialists. Comparison of anastrozole vs tamoxifen alone and in combination as neoadjuvant treatment of estrogen receptor-positive (ER+) operable breast cancer in postmenopausal women: the IMPACT trial. Breast Cancer Res Treat. 2003;83(suppl 1):S6. Abstract 1.IMPACT

5. Baum M, Buzdar AU, Cuzick J et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized data. Lancet 2002, 359, 2131-2139.

6. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early stage breast cancer. N Engl Med 2003, 349, 1793-1802.

7. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. NEJM 2004, 350 (11), 1081-1092.

8. Smith, Ian C., Heys, Steven D., Hutcheon, Andrew W., Miller, Iain D., Payne, Simon, Gilbert, Fiona J., Ah-See, Antoinne K., Eremin, Oleg, Walker, Leslie G., Sarkar, Tarun K., Eggleton, S. Peter, Ogston, Keith N.Neoadjuvant Chemotherapy in Breast Cancer: Significantly Enhanced Response With Docetaxel. J Clin Oncol 2002 20: 1456-1466.

9. Bear, Harry D., Anderson, Stewart, Brown, Ann, Smith, Roy, Mamounas, Eleftherios P., Fisher, Bernard, Margolese, Richard, Theoret, Heather, Soran, Atilla, Wickerham, D. Lawrence, Wolmark, Norman. The Effect on Tumor Response of Adding Sequential Preoperative Docetaxel to Preoperative Doxorubicin and Cyclophosphamide: Preliminary Results From National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2003 21: 4165-4174.

10. Hutcheon AW, Heys SD, Sarkar TK, Ogston KN, Eremin O, Walker LG, Miller ID University of Aberdeen, Scotland, United Kingdom Docetaxel primary chemotherapy in breast cancer: a five year update of the Aberdeen trial. Breast Cancer Res Treat. 2003;83(suppl 1):S6. Abstract 11.

Conflict of Interest:

None declared