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Editorial |
University Surgical Associates, APC 435, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02903
Correspondence: Address correspondence and reprint requests to: Blake Cady, MD; E-mail: bcady{at}usasurg.org
The article by Mendez et al.1 in this issue of Annals of Surgical Oncology is a reminder that all of our current surgical beliefs and convictions constantly need reanalysis and revision (or substantiation, as the case may be). Surgical oncologists should constantly review their operations, pathophysiological understanding, and conclusions so that we can provide leadership to the general surgical community regarding the diagnosis and management of cancers. We must be aware of disease trends, new data that accumulate, and new interpretations of and possibilities for surgical care. Articles such as this remind us to be alert to new assumptions. Our clinical and scientific field should be moving toward more sophistication in the selectivity and segmentation of patients and the rationalization of diagnosis and treatment, balancing risk and benefit, financial costs and savings, morbidity versus improved health, and complexity in contrast to simplification.
In breast cancer, remarkable changes have occurred in the past 15 years, largely because of widespread mammographic screening.2,3 This has resulted in much earlier disease presentation with smaller, lower-grade cancers and fewer lymph node metastases. This in turn has led to the abandonment of routine axillary dissection and the adoption of sentinel node biopsy to identify patients without lymph node metastases.4 Because <30% of patients now have any lymph node metastases and the number of positive nodes has decreased,3 sentinel node biopsy itself removes all the involved lymph nodes in >50% of cases with lymph node metastases. One distinct possibility that arises is that no more than sentinel node biopsy need be done, even if the nodes are involved with metastatic cells. Another possibility is that sentinel node biopsy may not be necessary if the likelihood of nodal metastases is very small, thus further simplifying our surgical approach to mammographically discovered, small, or special forms of breast cancer with an excellent prognosis.
This move toward simplifying and rationalizing our treatment of breast cancer has resulted in studying whether we can avoid adjuvant radiotherapy,5–7 adjuvant chemotherapy,8 or even adjuvant tamoxifen9 after surgery. For instance, Fyles et al.5 and Hughes et al.6 recently reported randomized trials comparing surgery and tamoxifen with or without radiotherapy for selected patients with estrogen receptor–positive cancers. Older patients (
60 or 70 years old) with smaller cancers (
1 cm or 2 cm) had either a nonsignificant difference or such a small significant difference in local recurrence (without differences in survival or mastectomy rates) that expensive and morbid postexcision radiotherapy may not be justified.7 Highly selected patients who were older (>50 years) and had smaller cancers ( 1.5 cm) that were not of high grade and were excised with an adequate surgical margin ( 1 cm) had only a 5% rate of local recurrence after avoiding radiotherapy in one report.10 Tabar et al.11 demonstrated that the great majority of patients with cancers 1.4 cm discovered by mammography have a 10-year survival rate that is so high that systemic therapy adds little except morbidity to all but a very few patients. Conversely, the small minority of such patients (7%) with a particular calcification pattern on mammography have such a poor prognosis that they actually create 37% of the mortality recorded in all patients with tumors of this small size. The latter patients may well be selected for aggressive systemic therapy, whereas the former can be spared.
These reports illustrate that primary cancer features or host features may be used to select suitability for avoiding or using adjuvant therapy. Simple clinical data may be used for major therapeutic decisions in a large proportion of current breast cancer patients in populations screened by mammography. Our obligation is to not overtreat excellent-prognosis breast cancers as much as it is to not undertreat poor-prognosis cancers.
Mendez and associates’1 report suggests that pathologic definition of selected good-prognosis cancers with a likelihood of lymph node metastasis <5% may enable such patients to avoid even the slight morbidity of sentinel node biopsy. The authors conclude that at this low rate of node metastasis, little is to be gained, for instance, by performing 100 sentinel node biopsies to find 5 cases with node metastases, some of which are only micrometastases or sub-micrometastases. Knowledge of such minor cellular spread may contribute to improved survival by use of adjuvant therapy in only the occasional case. It is interesting to note that the authors’ acceptance of a 5% chance of incomplete diagnostic and prognostic information is similar to the level of concern regarding the generally accepted false-negative rates of sentinel node biopsy or the risk of missing an isolated internal mammary lymph node metastasis by not biopsying that site. In these situations, the "missed" information translates to insignificant losses in the potential survival of patients because of the minimal nodal involvement of many cases, the use of primary tumor features (poor differentiation or lymph vessel invasion) for adjuvant therapy selection, and the relative ineffectiveness of much of our current systemic adjuvant treatment.
Many other categories of patients with breast cancer may fall at or below the authors’ 5% suitability criteria. For instance, tubular or other low-grade cancers that are small (T1a and T1b or 1.4 cm), which occur in patients >60 years of age, have an axillary nodal macrometastasis rate of <5%. Intermediate-grade cancers in patients aged >70 years that are small (T1a and T1b) generally also would demonstrate this low rate of node metastasis.12 Older patients with larger cancers that are estrogen receptor positive, although possibly having higher rates of node metastases, would not have their treatment with adjuvant tamoxifen changed by any additional information from a sentinel node biopsy, even if the nodes were positive. This has been emphasized by the minimal usefulness of added chemotherapy when older estrogen receptor–positive patients were treated with antiestrogens.13
In conclusion, this report by Mendez et al.1 adds to our sophistication in assessing patients for effective therapy, but it appropriately raises more interesting possibilities of a much larger pool of patients similarly advantaged by omitting sentinel node biopsy. Who would have thought, with the recent surge of enthusiasm for sentinel node biopsy in breast cancer for the obvious benefits of reduced morbidity yet highly accurate nodal information, that it would so soon come under scrutiny for revision and elimination? Such is the rapid progress of our management of breast cancer in this era of widespread screening mammography that we cannot predict what will be routine therapy in a few years. The rapidly expanding field of genetic analysis of cancers has already led to a report14 that a 70-gene array of the primary cancer provides more specific prognostic information than size or node metastases. Another report15 describes a two-gene ratio that accurately predicts the response to tamoxifen: this is perhaps more important to patients than information obtained by sentinel lymph node biopsy.
Furthermore, the burgeoning field of neoadjuvant chemotherapy16 has demonstrated that a complete pathologic response to initial chemotherapy is more prognostically important than size, node metastases, or grade. This indicates that a genetic test of the primary cancer determining such chemotherapy sensitivity would be more important than any traditional prognostic indicator, such as lymph node analysis.17
A tangential issue, of course, is the role of the lymphatic system.18,19 Current reports continue to emphasize that, with few exceptions, lymph node metastases, especially in the contemporary clinical situation of few lymph node metastases, are "indicators, but not governors" of distant metastasis and survival.19,20 Our past fixation on regional lymphatic removal to improve survival no longer seems pertinent, and willingness to challenge this old understanding in highly selected cases further opens the door to relegating the lymphatic and lymph node metastases to a background role in diagnosis and surgical treatment. This report should encourage yet more challenges to conventional assumptions regarding lymph node metastases and their removal.
Received for publication November 5, 2004. Accepted for publication November 12, 2004.
REFERENCES
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  K.-D. Yu, G.-H. Di, J. Wu, J.-S. Lu, K.-W. Shen, Z.-Z. Shen, and Z.-M. Shao Development and trends of surgical modalities for breast cancer in china: a review of 16-year data. Ann. Surg. Oncol., September 1, 2007; 14(9): 2502 - 2509. [Abstract] [Full Text] [PDF]
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B. Cady Regional Lymph Node Metastases; a Singular Manifestation of the Process of Clinical Metastases in Cancer: Contemporary Animal Research and Clinical Reports Suggest Unifying Concepts Ann. Surg. Oncol., June 1, 2007; 14(6): 1790 - 1800. [Abstract] [Full Text] [PDF]
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S. D. Nathanson, R. Slater, D. DeBruyn, A. Kapke, and M. Linden HER-2/neu Expression in Primary Breast Cancer With Sentinel Lymph Node Metastasis Ann. Surg. Oncol., February 1, 2006; 13(2): 205 - 213. [Abstract] [Full Text] [PDF]
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