The Impact of Microinvasion on Axillary Node Metastases and Survival in Patients With Intraductal Breast Cancer Jan H.
Wong, MD; Kelly H. Kopald, MD; Donald L. Morton, MD
\s=b\ A rational approach to the local treatment of intraductal breast cancer continues to generate considerable debate. However, the finding of an invasive component in intraductal breast cancer is widely regarded as an appropriate indication for axillary node dissection as part of the local treatment and staging of this disease. Despite this view, the natural history of patients with intraductal breast cancer with foci of microinvasion is poorly defined. Between 1965 and 1988,41 patients with this pathologic finding of intraductal carcinoma with foci of microinvasion were seen at the UCLA Medical Center. Twenty-three patients presented with mammographic abnormalities, while 17 patients presented with a palpable mass. One patient presented with Paget's disease of the nipple. Thirty-three patients underwent axillary node dissection as part of their local treatment. No lymph node metastases were identified. The median follow-up in 37 patients was 47 months. There have been no local recurrences and no deaths from recurrent breast cancer. Intraductal breast cancer associated with microinvasion appears to be an extremely favorable lesion with minimal risk of nodal metastases.
(Arch Surg. 1990;125:1298-1302)
increasing understanding of the natural history and biology of human breast cancer has led to significant advances in the local-regional therapy of this disease. Breastconserving surgery and radiation therapy have proven to be valid alternatives to mastectomy in most patients with inva¬ sive ductal breast cancer.12 However, considerable debate is still generated when clinicians are faced with defining a treat¬ ment philosophy for the spectrum of breast cancer in which the natural history and biology of the disease process is less _
Accepted for publication July 19,1990. From the Department of Surgery, Division of Surgical Oncology, John Wayne Cancer Clinic, Jonsson Comprehensive Cancer Center, UCLA School of Medicine (Drs Wong, Kopald, and Morton); and the Department of Surgery, Sepulveda (Calif) Veterans Affairs Medical Center (Dr Wong). Read before the 61st Annual Meeting of the Pacific Coast Surgical Association, Laguna Niguel, Calif, February 19,1990. Reprint requests to Department of Surgery, UCLA School of Medicine, 9th Floor Factor Bldg, Los Angeles, CA 90024 (Dr Wong).
clearly defined. Such is the case for intraductal carcinoma of the breast for which the treatment can range from complete excision alone3,4 to modified radical mastectomy.3,5"7 However, it would not be unreasonable to anticipate that the presence of microinvasion in patients with intraductal breast cancer would lead to a biologic behavior similar to infiltrating breast cancer and therefore, would justify similar treatment recom¬ mendations. Little information exists concerning the natural history of the pathologic entity of intraductal breast cancer with foci of microinvasion to support or negate this view. Data are lacking because intraductal breast cancer with microinvasion has generally been categorized with a spectrum of pathologic entities that includes intraductal breast cancer and infiltrating breast cancer less than 0.5 cm in diameter. This group of diseases has most commonly been referred to as "minimal breast cancer."8 Minimal breast cancer has been associated with a relatively good prognosis with a reported overall axillary node métastases rate of approximately 5%.9 However, the incidence of nodal métastases in patients with minimal breast cancer with invasion into the surrounding stroma has been reported to be as high as 31.5%.10 It is apparent that these histologie findings may represent a spec¬ trum of disease entities with different biologic behavior and a unique natural history. A survey conducted by the American College of Surgeons" identified approximately 10% of female breast cancers to be either in situ (1.9%) or minimally invasive carcinomas (8.4%). With the increasing use of screening mammography, a con¬ comitant increase is anticipated in the frequency with which these lesions will be diagnosed. To better define the natural history of intraductal breast cancer with microinvasion, we examined the presentation, treatment, and clinical course of patients with the pathologic diagnosis of intraductal breast cancer with microinvasion treated at the UCLA Medical Cen¬ ter. Our results suggest that patients with this pathologic entity are at low risk for axillary node métastases and can anticipate an excellent survival. PATIENTS AND METHODS From 1967 through 1988, 2244 patients with carcinoma of the breast (intraductal, lobular carcinoma in situ, infiltrating ductal car-
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Fig 2.—Age distribution of patients with intraductal breast cancer with foci of microinvasion. The mean age of patients was 54 years.
biopsy diagnosis revealed intraductal breast cancer with microinva¬ sion but who, on complete removal of the lesions, had more extensive, infiltrating breast cancer, and patients with infiltrating breast cancer and areas of microinvasion, were excluded from this analysis, as were patients with the diagnosis of lobular carcinoma in situ with foci of microinvasion.
RESULTS Patients
Fig 1.—Photomicrograph of intraductal breast cancer with foci of microinvasion. This figure represents largely an intraductal compo¬ nent of breast cancer with only a microscopic finding of a few tumor cells invading beyond the basement membrane of two ducts (arrows) (hematoxylin-eosin, original magnification 100).
cinoma, and infiltrating lobular carcinoma) were admitted to the UCLA Medical Center. The final pathologic diagnoses of these 2244 patients were individually reviewed along with a computerized search of the UCLA Medical Center Department of Pathology data¬ base. We identified 177 patients (8%) whose final pathologic diagnosis
intraductal breast cancer. An individual review of each of the pathologic records of these 177 patients revealed 41 patients with foci of microinvasion in addition to intraductal breast cancer. These pa¬ tients form the basis of this analysis. These 41 patients need to be distinguished from the substantially larger populations of patients with infiltrating breast cancer in whom carcinoma cells are readily identified in the surrounding stroma. Patients in whom the lesion was identified by mammography un¬ derwent localization prior to biopsy. A standard technique was used in which the mammographie abnormality was identified and localized both by needle and with the injection of méthylène blue dye. Follow¬ ing excision, presence of the abnormality was confirmed with stan¬ dard specimen mammography. An excisional biopsy was performed when a palpable mass was present. The definition of microinvasion ranges from a few cells penetrating the basement membrane to include tumors in which up to 10% of the specimen contains an invasive component.12 The diagnosis of intra¬ ductal breast cancer with microinvasion, in this report, was based on the findings of breast cancer cells confined to the duct system of the breast with only a microscopic focus of malignant cells invading beyond the basement membrane of the duct as determined by light microscopy (Fig 1), and was made only after extensive sectioning of the specimen. This pathologic diagnosis needs to be distinguished from the term minimally invasive microinvasion, which has com¬ monly been applied to invasive breast cancer less than 1 cm in diameter.1314 It should be emphasized that patients in whom the
Forty-one patients with intraductal breast cancer and mi¬ croinvasion were identified. These 41 patients represent few¬ er than 2% of all patients admitted to the UCLA Medical Center with the diagnosis of carcinoma of the breast during the study period. The patients were all women and ranged in age from 25 to 89 years (mean, 54 years) (Fig 2). Presentation The increasing use of screening mammography15 has re¬ sulted in an increasing diagnosis of "early" breast cancer. As shown below, more than half of the patients diagnosed with intraductal carcinoma with microinvasion presented with mammographie abnormalities alone that prompted biopsy: Presentation
Mammographie abnormality
was
No. of Patients
Microcalcifications
18 5 17 1
Nonpalpable mass Palpable mass Paget's disease
Microcalcifications were the most common abnormalities. One patient presented with Paget's disease of the nipple. The remaining 17 patients had palpable masses. The majority of these conditions were diagnosed prior to 1980. The palpable masses ranged from 1 to 4 cm (mean, 1.6 cm) in diameter. Treatment
Twenty-six patients underwent some form of mastectomy, as
indicated below:
Treatment Modified radical mastectomy
Simple mastectomy
Radical mastectomy
Breast-conserving surgery and radiation therapy
No. of Patients 22 2 2
9 1 1 the was most common proce¬ Modified radical mastectomy dure. However, two patients underwent radical mastectomy Local excision Whole breast irradiation
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and two underwent simple mastectomy alone. Nine patients underwent breast-conserving surgery, axillary node dissec¬ tion, and postoperative radiation therapy. One patient under¬ went local excision alone, and another underwent whole breast irradiation alone. The use of mastectomy in the treat¬ ment of intraductal breast cancer with microinvasion was as common before the increase in data supporting the efficacy of breast-conserving treatment for invasive breast cancer1,2 as after. Half the mastectomies were performed after the Na¬ tional Surgical Adjuvant Project for Breast and Bowel Can¬ cer protocol B-06 results were published.2 In contrast, the majority of patients undergoing breast-conserving surgery and radiation therapy did so after this report was published.
Outcome The
number of lymph nodes removed at the time of axillary node dissection was 25 (range, seven to 54), reflecting to some degree the extent of the axillary node dissection performed. No regional node involvement was identified in the 33 patients who underwent axillary lymph node dissec¬ tion. Four patients were unavailable for follow-up. The medi¬ an follow-up of the remaining 37 patients has been 47 months (range, 18 to 216 months). There have been no clinical axillary recurrences in patients who did not undergo axillary node dissection. Additionally, there have been no local recurrences in this group of patients. One patient died 10 years after treatment for her intraductal breast cancer with microinva¬ sion without evidence of recurrent breast cancer. No other patient died of recurrent breast cancer. mean
COMMENT This report describes the outcome of patients with intra¬
ductal carcinoma who, on light microscopy, have a component of microinvasion. The results show that intraductal breast cancer with microinvasion has not been associated with nodal métastases in our experience and is associated with an ex¬ tremely favorable prognosis. It should be emphasized that intraductal breast cancer with foci of microinvasion is dis¬ tinctly different from those breast cancers classified as mini¬ mally invasive breast cancer, a term that has commonly been used to characterize invasive breast cancers smaller than 1 cm in diameter.13,14 Our report does not attempt to address the question of accurately identifying this pathologic entity or the potential sampling error when performing a biopsy of either palpable or mammographie abnormalities. Because there were no deaths from breast cancer and no local recurrences, no benefit can be attributed to any of the modalities employed in treating this disease entity. The pathologic diagnosis of intraductal breast cancer with foci of microinvasion is based on the light microscopic evi¬ dence of cancer cells beyond the basement membrane of the normal duct. The pathologic criteria for intraductal breast cancer with microinvasion and the guidelines for diagnosis are far from precise. Some have applied the term microinvasive breast cancer to describe invasive tumors smaller than 0.5 cm in diameter,8 others to describe tumors smaller than 1.0 cm in diameter,13,14,16 and still others to describe certain histologie types of infiltrating cancer such as medullary, colloid, and tubular carcinomas.1T Although the diagnosis is subject to the interpretation of the pathologist, it is apparent that following extensive section of the specimen, a general consensus of this entity exists among our pathologists at UCLA. The incidence of intraductal breast cancer with microinva¬ sion is difficult to determine, largely because it has been grouped together with a number of pathologic entities under the term minimal breast cancer and to our knowledge, few institutions have had the opportunity to treat substantial numbers of these patients.18"22 Our experience indicates that
intraductal breast
cancer
with microinvasion is
a
finding, representing approximately
relatively
2% of all admitted to the UCLA Medical Center. Per¬ haps for this reason, the natural history ofthis entity has been poorly defined and has been assumed to have a biologic behav¬ ior similar to the usual infiltrating breast cancer. Mammogra¬ phy remains the most sensitive technique for the detection of early breast cancer.23 With evidence that detection of early breast cancer can influence outcome,24 it is anticipated that with the increasing use of screening mammography the inci¬ dence of mammographically identified breast cancers will increase. Patients with intraductal breast cancer and microinvasion may present with either a palpable mass or mammographie abnormalities. Increasing tumor size has repeatedly been demonstrated to be associated with a poorer prognosis as well as the presence or absence of nodal métastases.15,25 However, a palpable mass seemed not to have an adverse impact on outcome in this series of patients, suggesting that the histo¬ logie characteristics of the tumor as intraductal breast cancer with only a focus of microinvasion is a more important prog¬ nostic feature than tumor size. The incidence of lymph node involvement in patients with intraductal breast cancer with microinvasion is unknown. It has been suggested to be up to 5% in the spectrum of disease included under the term minimal breast cancer, as high as 5% in intraductal cancer alone,9 and up to 31.5%10 when "microin¬ vasion" is present. This later group may, in fact, include invasive breast cancer less than 1 cm in diameter. However, increasing reports indicate that the incidence of lymph node involvement is substantially less. In our experience, lymph node involvement is uncommon in patients with intraductal breast cancer with foci of microinvasion. Determining the optimal local treatment for intraductal breast cancer with microinvasion from our data is not possi¬ ble, since we have not experienced any treatment failures during the follow-up periods. Patients in this series under¬ went a variety of surgical procedures, with the addition of radiation therapy in certain instances without local recur¬ rence. The value of mastectomy in the local control of breast cancer and in intraductal breast cancer, in particular, has been well documented. Interestingly, a treatment philosophy for patients with intraductal breast cancer alone remains controversial although mastectomy is commonly recommend¬ ed as the prudent decision.7 However, the presence of mi¬ croinvasion seems to justify conservative breast surgery, axillary node dissection, and radiation therapy as an alterna¬ tive treatment. The demonstrated efficacy of mastectomy in the treatment of intraductal breast cancer seems to be direct¬ ly applicable to intraductal breast cancer with microinvasion, as are the results of prospective randomized trials comparing mastectomy and breast conserving surgery and radiothera¬ 1,z py. Our results suggest that the routine inclusion of lymph node dissection in the management of intraductal breast can¬ cer with microinvasion is not necessary. Because of the poten¬ tial sampling error when performing a biopsy, however, a reasonable approach to this entity might be to perform a complete excision of the tumor. If the final pathologic evalua¬ tion of all tissue identifies an infiltrating carcinoma, an axil¬ lary node dissection can subsequently be performed to evalu¬ ate what cancer stage the patient is in. It is apparent that evaluation of current treatment, both local and systemic, is best done in the setting of a clinical trial. Adjuvant chemotherapy has become an important compo¬ nent in the treatment of breast cancer.26 Attempts are now being made to duplicate the benefits achieved with adjuvant chemotherapy in patients with nodal métastases in patients with node-negative breast cancer. This, however, remains an uncommon breast cancer
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area
of continued controversy. It is apparent that in a disease
entity in which the natural history remains poorly defined, there is no role for evaluating the impact of adjuvant chemo¬ therapy outside of a clinical trial. In fact, our results suggest that the finding of foci of microinvasion in patients with
intraductal breast cancer is not ominous and the natural history of this histologie entity is more similar to intraductal breast cancer alone than invasive breast cancer. However, since the natural history of recurrent breast cancer extends well beyond the median follow-up of our report, continued long-term follow-up will be necessary to confirm our initial observations. These results, however, suggest that patients
with intraductal breast cancer with microinvasion probably should be distinguished from those with invasive breast can¬ cer when examining outcome following adjuvant chemothera¬ py. A better understanding of the natural history and biology of breast cancer will ultimately lead to optimal treatment recommendations.
This study was supported in part by grant CA 09010 from the National Institutes of Health, Bethesda, Md. Dr Wong is a recipient of the Cancer Development Reward from the Ameri¬ can Cancer Society.
References 1. Veronesi U, Banfi A, DelVecchio M, et al. Comparison of Halsted mastectomy with quadrantectomy, axillary dissection and radiotherapy in early breast cancer: long term results. Eur J Cancer Clin Oncol. 1986;22:1085-1089. 2. Fisher B, Bauer M, Margolese R, et al. Five year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of Cancer. N Engl J Med. 1985;312:665-673. 3. Farrow JH. The James Ewing lecture: current concepts in the detection and treatment of the earliest of the early breast cancers. Cancer. 1970;28:468\x=req-\ 477. 4. situ:
Lagios MD, Westdahl PR, Margolin FR, Rose MR. Duct carcinoma in relationship of extent of noninvasive disease to the frequency of occult invasion, multicentricity, lymph node metastases, and short term treatment
failures. Cancer. 1982;50:1309-1314. 5. Ashikari R, Huvos AG, Snyder RE. Prospective study of non-infiltrating carcinoma of the breast. Cancer. 1977;39:435-439. 6. Sunshine JA, Moseley HS, Fletcher WS, Krippaehne WK. Breast carcinoma in situ: a retrospective review of 112 cases with a minimum of 10 year follow up. Am J Surg. 1985;150:44-51. 7. Rosen PP, Braune DW, Kinne DE. The clinical significance of preinvasive breast carcinoma. Cancer. 1980;46:919-925. 8. Gallager HS, Martin JE. An orientation to the concept of minimal breast cancer. Cancer. 1971;28:1505-1507. 9. Jotti GS, Petit JY, Contesso G. Minimal breast cancer: a clinically meaningful term? Sem Oncol. 1986;13:384-392. 10. Santini D, Bassocchi F, Ricci M, et al. Prognostic consideration on minimal breast cancer. Breast Cancer Res Treat. 1986;8:104. 11. Bedwani R, Vana J, Rosner D, et al. Management and survival of female patients with 'minimal' breast cancer as observed in the long-term and short\x=req-\ term surveys of the American College of Surgeons. Cancer. 1981;47:2769-2778. 12. Schwartz GF, Pachefsky AS, Feig SA, et al. Clinically occult breast cancer: multicentricity and implications for treatment. Ann Surg. 1980;191: 8-12. 13. Frazier TG, Copeland EM, Gallager HS, Paulus DD, White EC. Progno-
sis and treatment in minimal breast cancer. Am J Surg. 1977;133:697-701. 14. Ackerman LV, Katzenstein AL. The concept of minimal breast cancer and the pathologist's role in the diagnosis of 'early carcinoma.' Cancer.
1977;39:2755-2763.
15. Lewis JD, Milbrath JR, Shaffer KA, DeCosse JJ. Implications of suspicious findings in breast cancer screening. Arch Surg. 1975;110:903-907. 16. McDivitt RW. Breast carcinoma. Hum Pathol. 1978;9:3-21. 17. Hutter RVP. The pathologist's role in minimal breast cancer. Cancer.
1971;28:1527-1536.
18. Schwartz GF, Feig SA, Rosenber AL, et al. Staging and treatment of clinically occult breast cancer. Cancer. 1984;53:1379-1384. 19. Marrugu G, Jolly PC, Hall MM. Nonpalpable breast cancer needle localization biopsy for diagnosis and considerations for treatment. Am J Surg.
1986;151:599-602. 20. Poole GV, Choplin RH, Sterchi JM, Lerinbach LB, Myers RT. Occult lesions of the breast. Surg Gynecol Obstet. 1986;163:107-110. 21. Rodes ND, Lopez MJ, Pearson DK, Blackwell CW, Lankford HD. The a 5 to 10 year follow-up study. Cancer. 1986;57:581-585. 22. Silverstein MJ, Gamagami P, Rosser RJ, et al. Hooked wire directed breast biopsy and over penetrated mammography. Cancer. 1987;59:715-722. 23. Wertheimer MD, Costanza ME, Dodson TF, D'Orsi C, Pastiden H, Zapka JG. Increasing the effort toward breast cancer detection. JAMA.
impact of breast cancer screening on survival:
1986;255:1311-1315. 24. Shapiro S, Venet W, Strax P, Venet L, Roeser R. Ten to fourteen year effect of screening on breast cancer mortality. J Nati Cancer Inst. 1982;69:349\x=req-\ 355. 25. Koscielny S, Tubiana M, Le MG, Mourisse H, Contesso G, Sarrazin D. Breast cancer: relationship between the size of the primary tumour and the probability of metastatic dissemination. Br J Cancer. 1984;49:709-715. 26. Bonadonna G, Valagussa P. Adjuvant systemic therapy for resectable breast cancer. J Clin Oncol. 1985;3:259-275.
Discussion R. MARK Vetto,MD, Portland, Ore: Not so long ago, derision greeted surgeons who suggested that a lumpectomy might be used to treat breast cancer. Perhaps this attempt to eliminate axillary dissec¬ tion in a specific class of breast cancer is the next step. However, the earlier tumors that we see today and the increasing ways in which we categorize them in terms of size, invasion, type, endocrine markers, flow cytometry, and extent of regional métasta¬ ses if any, have made the surgical management decisions much more
difficult. Intraductal carcinoma without invasion is multifocal in 50% of the cases and will eventually recur as cancer in the same breast in 30% to 50% of the cases. Intraductal cancer does not require axillary dissection, but nevertheless exhibits axillary métastases in 1% to 5% of patients. In our institution, intraductal carcinoma is commonly treated with local resection and radiation, and many of these patients qualify for the National Surgical Adjuvant Project for Breast and Bowel Cancer B-17 protocol. However, some of our patients undergo local resection alone, or total mastectomy, or occasionally modified radical mastectomy. At the other extreme, minimally invasive ductal cancers, usually detected by screening mammography, when not treated with modi¬ fied radical resection are treated with local excision, staging axillary dissection, and breast radiation. The authors state that the incidence of axillary métastases in this group of patients is 5%, although others have reported a higher incidence. The authors propose to establish a new category of patients with
ductal carcinoma in whom the tumor is not intraductal and minimally invasive, but is microinvasive and has not exhibited axillary métasta¬ ses in the 37 cases presented. This is indeed a noble effort to eliminate axillary dissection, but there are several criticisms. Microinvasion is difficult to unequivocally establish and is subject to sampling error. Even intraductal in situ tumors have an incidence of axillary metastasis that may be related to missing an invasive area when cutting the specimen. Four of the 41 patients described were unavailable for follow-up, which represents a possible undiscovered recurrence rate of 10%. There is some question about the length of follow-up despite the median of 47 months, since nearly two thirds of the patients had a nonpalpable tumor that required localization and therefore must have been of a more recent origin. In fact, one of the patients was followed up for 18 months. On the positive side, if the incidence of axillary métastases with small ductal carcinomas is 5% or even 10%, for every 100 axillary dissections we do, 90 or 95 are not necessary. We certainly ought to try to do better than that. So the real question in my mind is whether we should continue to indiscriminately perform staging axillary dissection for small ductal cancers when physical examination of the axilla yields no results and other risk factors are absent. Dr Wong, I am very attracted to the notion that we ought to inch up to where we do not perform so many "negative axillary dissections," and perhaps the identification of the microinvasive ductal tumor is the first inch. Certainly, it can be no
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greater than an inch since tumors with the degree of invasion you describe represent only 2% of the breast pool at your institution. Balazs I. BODAI, MD, Carmichael, Calif: At Kaiser Permanente in Sacramento (Calif), we treat upwards of 400 breast cancers per are currently doing about 25 000 screening mammograms annually, soon to reach 35 000. I see these patients, probably approximately one every other month. I do not know what my colleagues are seeing, but I have certainly been excited by this study to review our experience. Despite the fact that the recurrence rate is as low as it is, do you still offer all the options to the patient for the treatment of breast cancer? That is, from doing nothing, ie, observation, to performing a modified
year. We
radical mastectomy, and where do you feel that their best choice would lie? Would your recommendations be tempered at all by the patient's age, that is, would you recommend it for a 30-year-old woman as opposed to a 60-year-old woman? RICHARD P. SAIK, MD, La Jolla, Calif: The authors have a unique sampling of 22 women who underwent mastectomy for minimal can¬ cer. I wonder if they reviewed the pathologic specimens to see if there were other foci of cancer or microinvasion in other areas of the breast. ARMANDO E. GIULIANO, MD, Los Angeles, Calif: Microinvasive cancer is invasive. The presentation would lead us to believe that intraductal and microinvasive are the same. Microinvasive cancer has shown that it has the ability to penetrate the basement membrane and metastasize. Along the spectrum of breast cancers, we know that the smaller the cancer, the less likely it is to have positive nodes. It is safe to assume that these are early lesions with a low incidence of positive nodes, but we should perform an axillary dissection. A negative axillary dissection is not an unnecessary procedure. It tells you whether there are lymph node métastases or not. It is not therapeutic, but then again, the removal of microscopically positive nodes may not be therapeutic. Are you really advocating that if a woman comes in with a palpable mass (as 17 of your patients did) and she has microinvasion, we do not perform an axillary dissection? Clare G. Peterson, MD, Portland, Ore: Invasive cancer is invasive cancer. I have spent my life in surgery regretting the lost opportunities to contain small malignancies by adequate en bloc operations. There should not be much confusion about the fact that microinvasion of breast cancer with breakthrough of the basement membrane is truly invasive infiltrating carcinoma of the breast with all the metastatic capabilities of such a lesion. The message of this report, demonstrating microinvasion (small, early, invasive cancers) treated by en bloc procedures (total mastec¬ tomy or modified radical mastectomy), shows excellent survival re¬ sults free of cancer at this time. This is vindication of the en bloc principle in the treatment of invasive breast cancer—the clinical arguments and dilemmas remain¬ ing being related to the true staging of the cancer before operation, and the extent and completeness of the en bloc resectional procedure carried out. I cannot agree with the categorical and contradictory statement that, "in this setting," axillary node dissection is unwarranted. Dr Morton: Our data clearly indicate that axillary lymph node métastases and recurrence are very rare in women who have microin¬ vasive intraductal carcinoma. Thus, if one can unequivocally make
such a diagnosis, axillary node dissection does not appear to be indicated. We agree that this conclusion must be regarded as prelimi¬ nary until more data are accumulated. We cannot be dogmatic when the total number of such patients is only 41. None of these patients had either lymph node métastases or recurrence after a 47-month median observation period, and it is unlikely that larger numbers or longer follow-up will change this conclusion. Nevertheless, we chal¬ lenge you to review your own experience with this entity and prove us wrong. One important question that our study does not answer nor at¬ tempt to answer relates to the multifocal nature of breast intraductal carcinoma and the frequency with which the initial biopsy results will be interpreted as microinvasive intraductal carcinoma, and, after subsequent mastectomy, other areas of frankly invasive intraductal carcinoma will be found with examination of the entire breast. Such patients would not have been included in our review because we were searching for cases of intraductal carcinoma with microinvasion only. Therefore, we must know how frequently pathologic examination of the entire mastectomy specimen leads to a modification of the initial
diagnosis.
Recurrence time is inversely proportional to the size of the lesion. That is, a smaller lesion may take longer to recur than a larger one. We need data from more centers and a longer follow-up before changing our routine treatment from a properly conducted procedure that treats the entire breast by mastectomy or a small procedure in which the entire breast is treated by radiation. This study never implies that the whole breast should not be treated. It only indicates that the patients with intraductal breast cancer and microinvasion have an excellent prognosis and a low incidence of axillary node métastases; all patients in this group except for one had treatment of the entire breast. Since we had up to 20 years of follow-up in some of our cases, I doubt if longer follow-up will change the basic conclusion. Dr Bodai, we do discuss all options for therapy with the patients and advise mastectomy or local resection and radiation. Age cannot be a primary consideration in terms of such discussions; the elderly woman is often as anxious to have breast preservation as a young woman.
Dr Saik, we did not get out the 177 cases and go through the breast by serial sections to look for additional areas of microinvasion. We
would not have included those cases in our review in which additional areas of frankly invasive carcinoma were found by the pathologists in the mastectomy specimens. Dr Peterson, it is important to point out that when no treatment failures occur, no benefit can be attributed to any treatment modal¬ ity. It does not support the en bloc principle, but rather, if anything, suggests the equivalent efficacy of "lesser procedures" in this patho¬
logic entity. Dr Giuliano, one has to either take the position that one will routinely perform an axillary dissection on every case such as this, or be committed to go back and do an axillary dissection if, on pathologic examination of the entire specimen, other areas of frank invasion are found. Until we know how frequently the diagnosis will be changed by examination of the entire specimen, it may be inappropriate to per¬ form an axillary dissection at the initial operation when this informa¬ tion may change the treatment plan.
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Wong, MD; Kelly H. Kopald, MD; Donald L. Morton, MD
\s=b\ A rational approach to the local treatment of intraductal breast cancer continues to generate considerable debate. However, the finding of an invasive component in intraductal breast cancer is widely regarded as an appropriate indication for axillary node dissection as part of the local treatment and staging of this disease. Despite this view, the natural history of patients with intraductal breast cancer with foci of microinvasion is poorly defined. Between 1965 and 1988,41 patients with this pathologic finding of intraductal carcinoma with foci of microinvasion were seen at the UCLA Medical Center. Twenty-three patients presented with mammographic abnormalities, while 17 patients presented with a palpable mass. One patient presented with Paget's disease of the nipple. Thirty-three patients underwent axillary node dissection as part of their local treatment. No lymph node metastases were identified. The median follow-up in 37 patients was 47 months. There have been no local recurrences and no deaths from recurrent breast cancer. Intraductal breast cancer associated with microinvasion appears to be an extremely favorable lesion with minimal risk of nodal metastases.
(Arch Surg. 1990;125:1298-1302)
increasing understanding of the natural history and biology of human breast cancer has led to significant advances in the local-regional therapy of this disease. Breastconserving surgery and radiation therapy have proven to be valid alternatives to mastectomy in most patients with inva¬ sive ductal breast cancer.12 However, considerable debate is still generated when clinicians are faced with defining a treat¬ ment philosophy for the spectrum of breast cancer in which the natural history and biology of the disease process is less _
Accepted for publication July 19,1990. From the Department of Surgery, Division of Surgical Oncology, John Wayne Cancer Clinic, Jonsson Comprehensive Cancer Center, UCLA School of Medicine (Drs Wong, Kopald, and Morton); and the Department of Surgery, Sepulveda (Calif) Veterans Affairs Medical Center (Dr Wong). Read before the 61st Annual Meeting of the Pacific Coast Surgical Association, Laguna Niguel, Calif, February 19,1990. Reprint requests to Department of Surgery, UCLA School of Medicine, 9th Floor Factor Bldg, Los Angeles, CA 90024 (Dr Wong).
clearly defined. Such is the case for intraductal carcinoma of the breast for which the treatment can range from complete excision alone3,4 to modified radical mastectomy.3,5"7 However, it would not be unreasonable to anticipate that the presence of microinvasion in patients with intraductal breast cancer would lead to a biologic behavior similar to infiltrating breast cancer and therefore, would justify similar treatment recom¬ mendations. Little information exists concerning the natural history of the pathologic entity of intraductal breast cancer with foci of microinvasion to support or negate this view. Data are lacking because intraductal breast cancer with microinvasion has generally been categorized with a spectrum of pathologic entities that includes intraductal breast cancer and infiltrating breast cancer less than 0.5 cm in diameter. This group of diseases has most commonly been referred to as "minimal breast cancer."8 Minimal breast cancer has been associated with a relatively good prognosis with a reported overall axillary node métastases rate of approximately 5%.9 However, the incidence of nodal métastases in patients with minimal breast cancer with invasion into the surrounding stroma has been reported to be as high as 31.5%.10 It is apparent that these histologie findings may represent a spec¬ trum of disease entities with different biologic behavior and a unique natural history. A survey conducted by the American College of Surgeons" identified approximately 10% of female breast cancers to be either in situ (1.9%) or minimally invasive carcinomas (8.4%). With the increasing use of screening mammography, a con¬ comitant increase is anticipated in the frequency with which these lesions will be diagnosed. To better define the natural history of intraductal breast cancer with microinvasion, we examined the presentation, treatment, and clinical course of patients with the pathologic diagnosis of intraductal breast cancer with microinvasion treated at the UCLA Medical Cen¬ ter. Our results suggest that patients with this pathologic entity are at low risk for axillary node métastases and can anticipate an excellent survival. PATIENTS AND METHODS From 1967 through 1988, 2244 patients with carcinoma of the breast (intraductal, lobular carcinoma in situ, infiltrating ductal car-
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Fig 2.—Age distribution of patients with intraductal breast cancer with foci of microinvasion. The mean age of patients was 54 years.
biopsy diagnosis revealed intraductal breast cancer with microinva¬ sion but who, on complete removal of the lesions, had more extensive, infiltrating breast cancer, and patients with infiltrating breast cancer and areas of microinvasion, were excluded from this analysis, as were patients with the diagnosis of lobular carcinoma in situ with foci of microinvasion.
RESULTS Patients
Fig 1.—Photomicrograph of intraductal breast cancer with foci of microinvasion. This figure represents largely an intraductal compo¬ nent of breast cancer with only a microscopic finding of a few tumor cells invading beyond the basement membrane of two ducts (arrows) (hematoxylin-eosin, original magnification 100).
cinoma, and infiltrating lobular carcinoma) were admitted to the UCLA Medical Center. The final pathologic diagnoses of these 2244 patients were individually reviewed along with a computerized search of the UCLA Medical Center Department of Pathology data¬ base. We identified 177 patients (8%) whose final pathologic diagnosis
intraductal breast cancer. An individual review of each of the pathologic records of these 177 patients revealed 41 patients with foci of microinvasion in addition to intraductal breast cancer. These pa¬ tients form the basis of this analysis. These 41 patients need to be distinguished from the substantially larger populations of patients with infiltrating breast cancer in whom carcinoma cells are readily identified in the surrounding stroma. Patients in whom the lesion was identified by mammography un¬ derwent localization prior to biopsy. A standard technique was used in which the mammographie abnormality was identified and localized both by needle and with the injection of méthylène blue dye. Follow¬ ing excision, presence of the abnormality was confirmed with stan¬ dard specimen mammography. An excisional biopsy was performed when a palpable mass was present. The definition of microinvasion ranges from a few cells penetrating the basement membrane to include tumors in which up to 10% of the specimen contains an invasive component.12 The diagnosis of intra¬ ductal breast cancer with microinvasion, in this report, was based on the findings of breast cancer cells confined to the duct system of the breast with only a microscopic focus of malignant cells invading beyond the basement membrane of the duct as determined by light microscopy (Fig 1), and was made only after extensive sectioning of the specimen. This pathologic diagnosis needs to be distinguished from the term minimally invasive microinvasion, which has com¬ monly been applied to invasive breast cancer less than 1 cm in diameter.1314 It should be emphasized that patients in whom the
Forty-one patients with intraductal breast cancer and mi¬ croinvasion were identified. These 41 patients represent few¬ er than 2% of all patients admitted to the UCLA Medical Center with the diagnosis of carcinoma of the breast during the study period. The patients were all women and ranged in age from 25 to 89 years (mean, 54 years) (Fig 2). Presentation The increasing use of screening mammography15 has re¬ sulted in an increasing diagnosis of "early" breast cancer. As shown below, more than half of the patients diagnosed with intraductal carcinoma with microinvasion presented with mammographie abnormalities alone that prompted biopsy: Presentation
Mammographie abnormality
was
No. of Patients
Microcalcifications
18 5 17 1
Nonpalpable mass Palpable mass Paget's disease
Microcalcifications were the most common abnormalities. One patient presented with Paget's disease of the nipple. The remaining 17 patients had palpable masses. The majority of these conditions were diagnosed prior to 1980. The palpable masses ranged from 1 to 4 cm (mean, 1.6 cm) in diameter. Treatment
Twenty-six patients underwent some form of mastectomy, as
indicated below:
Treatment Modified radical mastectomy
Simple mastectomy
Radical mastectomy
Breast-conserving surgery and radiation therapy
No. of Patients 22 2 2
9 1 1 the was most common proce¬ Modified radical mastectomy dure. However, two patients underwent radical mastectomy Local excision Whole breast irradiation
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and two underwent simple mastectomy alone. Nine patients underwent breast-conserving surgery, axillary node dissec¬ tion, and postoperative radiation therapy. One patient under¬ went local excision alone, and another underwent whole breast irradiation alone. The use of mastectomy in the treat¬ ment of intraductal breast cancer with microinvasion was as common before the increase in data supporting the efficacy of breast-conserving treatment for invasive breast cancer1,2 as after. Half the mastectomies were performed after the Na¬ tional Surgical Adjuvant Project for Breast and Bowel Can¬ cer protocol B-06 results were published.2 In contrast, the majority of patients undergoing breast-conserving surgery and radiation therapy did so after this report was published.
Outcome The
number of lymph nodes removed at the time of axillary node dissection was 25 (range, seven to 54), reflecting to some degree the extent of the axillary node dissection performed. No regional node involvement was identified in the 33 patients who underwent axillary lymph node dissec¬ tion. Four patients were unavailable for follow-up. The medi¬ an follow-up of the remaining 37 patients has been 47 months (range, 18 to 216 months). There have been no clinical axillary recurrences in patients who did not undergo axillary node dissection. Additionally, there have been no local recurrences in this group of patients. One patient died 10 years after treatment for her intraductal breast cancer with microinva¬ sion without evidence of recurrent breast cancer. No other patient died of recurrent breast cancer. mean
COMMENT This report describes the outcome of patients with intra¬
ductal carcinoma who, on light microscopy, have a component of microinvasion. The results show that intraductal breast cancer with microinvasion has not been associated with nodal métastases in our experience and is associated with an ex¬ tremely favorable prognosis. It should be emphasized that intraductal breast cancer with foci of microinvasion is dis¬ tinctly different from those breast cancers classified as mini¬ mally invasive breast cancer, a term that has commonly been used to characterize invasive breast cancers smaller than 1 cm in diameter.13,14 Our report does not attempt to address the question of accurately identifying this pathologic entity or the potential sampling error when performing a biopsy of either palpable or mammographie abnormalities. Because there were no deaths from breast cancer and no local recurrences, no benefit can be attributed to any of the modalities employed in treating this disease entity. The pathologic diagnosis of intraductal breast cancer with foci of microinvasion is based on the light microscopic evi¬ dence of cancer cells beyond the basement membrane of the normal duct. The pathologic criteria for intraductal breast cancer with microinvasion and the guidelines for diagnosis are far from precise. Some have applied the term microinvasive breast cancer to describe invasive tumors smaller than 0.5 cm in diameter,8 others to describe tumors smaller than 1.0 cm in diameter,13,14,16 and still others to describe certain histologie types of infiltrating cancer such as medullary, colloid, and tubular carcinomas.1T Although the diagnosis is subject to the interpretation of the pathologist, it is apparent that following extensive section of the specimen, a general consensus of this entity exists among our pathologists at UCLA. The incidence of intraductal breast cancer with microinva¬ sion is difficult to determine, largely because it has been grouped together with a number of pathologic entities under the term minimal breast cancer and to our knowledge, few institutions have had the opportunity to treat substantial numbers of these patients.18"22 Our experience indicates that
intraductal breast
cancer
with microinvasion is
a
finding, representing approximately
relatively
2% of all admitted to the UCLA Medical Center. Per¬ haps for this reason, the natural history ofthis entity has been poorly defined and has been assumed to have a biologic behav¬ ior similar to the usual infiltrating breast cancer. Mammogra¬ phy remains the most sensitive technique for the detection of early breast cancer.23 With evidence that detection of early breast cancer can influence outcome,24 it is anticipated that with the increasing use of screening mammography the inci¬ dence of mammographically identified breast cancers will increase. Patients with intraductal breast cancer and microinvasion may present with either a palpable mass or mammographie abnormalities. Increasing tumor size has repeatedly been demonstrated to be associated with a poorer prognosis as well as the presence or absence of nodal métastases.15,25 However, a palpable mass seemed not to have an adverse impact on outcome in this series of patients, suggesting that the histo¬ logie characteristics of the tumor as intraductal breast cancer with only a focus of microinvasion is a more important prog¬ nostic feature than tumor size. The incidence of lymph node involvement in patients with intraductal breast cancer with microinvasion is unknown. It has been suggested to be up to 5% in the spectrum of disease included under the term minimal breast cancer, as high as 5% in intraductal cancer alone,9 and up to 31.5%10 when "microin¬ vasion" is present. This later group may, in fact, include invasive breast cancer less than 1 cm in diameter. However, increasing reports indicate that the incidence of lymph node involvement is substantially less. In our experience, lymph node involvement is uncommon in patients with intraductal breast cancer with foci of microinvasion. Determining the optimal local treatment for intraductal breast cancer with microinvasion from our data is not possi¬ ble, since we have not experienced any treatment failures during the follow-up periods. Patients in this series under¬ went a variety of surgical procedures, with the addition of radiation therapy in certain instances without local recur¬ rence. The value of mastectomy in the local control of breast cancer and in intraductal breast cancer, in particular, has been well documented. Interestingly, a treatment philosophy for patients with intraductal breast cancer alone remains controversial although mastectomy is commonly recommend¬ ed as the prudent decision.7 However, the presence of mi¬ croinvasion seems to justify conservative breast surgery, axillary node dissection, and radiation therapy as an alterna¬ tive treatment. The demonstrated efficacy of mastectomy in the treatment of intraductal breast cancer seems to be direct¬ ly applicable to intraductal breast cancer with microinvasion, as are the results of prospective randomized trials comparing mastectomy and breast conserving surgery and radiothera¬ 1,z py. Our results suggest that the routine inclusion of lymph node dissection in the management of intraductal breast can¬ cer with microinvasion is not necessary. Because of the poten¬ tial sampling error when performing a biopsy, however, a reasonable approach to this entity might be to perform a complete excision of the tumor. If the final pathologic evalua¬ tion of all tissue identifies an infiltrating carcinoma, an axil¬ lary node dissection can subsequently be performed to evalu¬ ate what cancer stage the patient is in. It is apparent that evaluation of current treatment, both local and systemic, is best done in the setting of a clinical trial. Adjuvant chemotherapy has become an important compo¬ nent in the treatment of breast cancer.26 Attempts are now being made to duplicate the benefits achieved with adjuvant chemotherapy in patients with nodal métastases in patients with node-negative breast cancer. This, however, remains an uncommon breast cancer
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area
of continued controversy. It is apparent that in a disease
entity in which the natural history remains poorly defined, there is no role for evaluating the impact of adjuvant chemo¬ therapy outside of a clinical trial. In fact, our results suggest that the finding of foci of microinvasion in patients with
intraductal breast cancer is not ominous and the natural history of this histologie entity is more similar to intraductal breast cancer alone than invasive breast cancer. However, since the natural history of recurrent breast cancer extends well beyond the median follow-up of our report, continued long-term follow-up will be necessary to confirm our initial observations. These results, however, suggest that patients
with intraductal breast cancer with microinvasion probably should be distinguished from those with invasive breast can¬ cer when examining outcome following adjuvant chemothera¬ py. A better understanding of the natural history and biology of breast cancer will ultimately lead to optimal treatment recommendations.
This study was supported in part by grant CA 09010 from the National Institutes of Health, Bethesda, Md. Dr Wong is a recipient of the Cancer Development Reward from the Ameri¬ can Cancer Society.
References 1. Veronesi U, Banfi A, DelVecchio M, et al. Comparison of Halsted mastectomy with quadrantectomy, axillary dissection and radiotherapy in early breast cancer: long term results. Eur J Cancer Clin Oncol. 1986;22:1085-1089. 2. Fisher B, Bauer M, Margolese R, et al. Five year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of Cancer. N Engl J Med. 1985;312:665-673. 3. Farrow JH. The James Ewing lecture: current concepts in the detection and treatment of the earliest of the early breast cancers. Cancer. 1970;28:468\x=req-\ 477. 4. situ:
Lagios MD, Westdahl PR, Margolin FR, Rose MR. Duct carcinoma in relationship of extent of noninvasive disease to the frequency of occult invasion, multicentricity, lymph node metastases, and short term treatment
failures. Cancer. 1982;50:1309-1314. 5. Ashikari R, Huvos AG, Snyder RE. Prospective study of non-infiltrating carcinoma of the breast. Cancer. 1977;39:435-439. 6. Sunshine JA, Moseley HS, Fletcher WS, Krippaehne WK. Breast carcinoma in situ: a retrospective review of 112 cases with a minimum of 10 year follow up. Am J Surg. 1985;150:44-51. 7. Rosen PP, Braune DW, Kinne DE. The clinical significance of preinvasive breast carcinoma. Cancer. 1980;46:919-925. 8. Gallager HS, Martin JE. An orientation to the concept of minimal breast cancer. Cancer. 1971;28:1505-1507. 9. Jotti GS, Petit JY, Contesso G. Minimal breast cancer: a clinically meaningful term? Sem Oncol. 1986;13:384-392. 10. Santini D, Bassocchi F, Ricci M, et al. Prognostic consideration on minimal breast cancer. Breast Cancer Res Treat. 1986;8:104. 11. Bedwani R, Vana J, Rosner D, et al. Management and survival of female patients with 'minimal' breast cancer as observed in the long-term and short\x=req-\ term surveys of the American College of Surgeons. Cancer. 1981;47:2769-2778. 12. Schwartz GF, Pachefsky AS, Feig SA, et al. Clinically occult breast cancer: multicentricity and implications for treatment. Ann Surg. 1980;191: 8-12. 13. Frazier TG, Copeland EM, Gallager HS, Paulus DD, White EC. Progno-
sis and treatment in minimal breast cancer. Am J Surg. 1977;133:697-701. 14. Ackerman LV, Katzenstein AL. The concept of minimal breast cancer and the pathologist's role in the diagnosis of 'early carcinoma.' Cancer.
1977;39:2755-2763.
15. Lewis JD, Milbrath JR, Shaffer KA, DeCosse JJ. Implications of suspicious findings in breast cancer screening. Arch Surg. 1975;110:903-907. 16. McDivitt RW. Breast carcinoma. Hum Pathol. 1978;9:3-21. 17. Hutter RVP. The pathologist's role in minimal breast cancer. Cancer.
1971;28:1527-1536.
18. Schwartz GF, Feig SA, Rosenber AL, et al. Staging and treatment of clinically occult breast cancer. Cancer. 1984;53:1379-1384. 19. Marrugu G, Jolly PC, Hall MM. Nonpalpable breast cancer needle localization biopsy for diagnosis and considerations for treatment. Am J Surg.
1986;151:599-602. 20. Poole GV, Choplin RH, Sterchi JM, Lerinbach LB, Myers RT. Occult lesions of the breast. Surg Gynecol Obstet. 1986;163:107-110. 21. Rodes ND, Lopez MJ, Pearson DK, Blackwell CW, Lankford HD. The a 5 to 10 year follow-up study. Cancer. 1986;57:581-585. 22. Silverstein MJ, Gamagami P, Rosser RJ, et al. Hooked wire directed breast biopsy and over penetrated mammography. Cancer. 1987;59:715-722. 23. Wertheimer MD, Costanza ME, Dodson TF, D'Orsi C, Pastiden H, Zapka JG. Increasing the effort toward breast cancer detection. JAMA.
impact of breast cancer screening on survival:
1986;255:1311-1315. 24. Shapiro S, Venet W, Strax P, Venet L, Roeser R. Ten to fourteen year effect of screening on breast cancer mortality. J Nati Cancer Inst. 1982;69:349\x=req-\ 355. 25. Koscielny S, Tubiana M, Le MG, Mourisse H, Contesso G, Sarrazin D. Breast cancer: relationship between the size of the primary tumour and the probability of metastatic dissemination. Br J Cancer. 1984;49:709-715. 26. Bonadonna G, Valagussa P. Adjuvant systemic therapy for resectable breast cancer. J Clin Oncol. 1985;3:259-275.
Discussion R. MARK Vetto,MD, Portland, Ore: Not so long ago, derision greeted surgeons who suggested that a lumpectomy might be used to treat breast cancer. Perhaps this attempt to eliminate axillary dissec¬ tion in a specific class of breast cancer is the next step. However, the earlier tumors that we see today and the increasing ways in which we categorize them in terms of size, invasion, type, endocrine markers, flow cytometry, and extent of regional métasta¬ ses if any, have made the surgical management decisions much more
difficult. Intraductal carcinoma without invasion is multifocal in 50% of the cases and will eventually recur as cancer in the same breast in 30% to 50% of the cases. Intraductal cancer does not require axillary dissection, but nevertheless exhibits axillary métastases in 1% to 5% of patients. In our institution, intraductal carcinoma is commonly treated with local resection and radiation, and many of these patients qualify for the National Surgical Adjuvant Project for Breast and Bowel Cancer B-17 protocol. However, some of our patients undergo local resection alone, or total mastectomy, or occasionally modified radical mastectomy. At the other extreme, minimally invasive ductal cancers, usually detected by screening mammography, when not treated with modi¬ fied radical resection are treated with local excision, staging axillary dissection, and breast radiation. The authors state that the incidence of axillary métastases in this group of patients is 5%, although others have reported a higher incidence. The authors propose to establish a new category of patients with
ductal carcinoma in whom the tumor is not intraductal and minimally invasive, but is microinvasive and has not exhibited axillary métasta¬ ses in the 37 cases presented. This is indeed a noble effort to eliminate axillary dissection, but there are several criticisms. Microinvasion is difficult to unequivocally establish and is subject to sampling error. Even intraductal in situ tumors have an incidence of axillary metastasis that may be related to missing an invasive area when cutting the specimen. Four of the 41 patients described were unavailable for follow-up, which represents a possible undiscovered recurrence rate of 10%. There is some question about the length of follow-up despite the median of 47 months, since nearly two thirds of the patients had a nonpalpable tumor that required localization and therefore must have been of a more recent origin. In fact, one of the patients was followed up for 18 months. On the positive side, if the incidence of axillary métastases with small ductal carcinomas is 5% or even 10%, for every 100 axillary dissections we do, 90 or 95 are not necessary. We certainly ought to try to do better than that. So the real question in my mind is whether we should continue to indiscriminately perform staging axillary dissection for small ductal cancers when physical examination of the axilla yields no results and other risk factors are absent. Dr Wong, I am very attracted to the notion that we ought to inch up to where we do not perform so many "negative axillary dissections," and perhaps the identification of the microinvasive ductal tumor is the first inch. Certainly, it can be no
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greater than an inch since tumors with the degree of invasion you describe represent only 2% of the breast pool at your institution. Balazs I. BODAI, MD, Carmichael, Calif: At Kaiser Permanente in Sacramento (Calif), we treat upwards of 400 breast cancers per are currently doing about 25 000 screening mammograms annually, soon to reach 35 000. I see these patients, probably approximately one every other month. I do not know what my colleagues are seeing, but I have certainly been excited by this study to review our experience. Despite the fact that the recurrence rate is as low as it is, do you still offer all the options to the patient for the treatment of breast cancer? That is, from doing nothing, ie, observation, to performing a modified
year. We
radical mastectomy, and where do you feel that their best choice would lie? Would your recommendations be tempered at all by the patient's age, that is, would you recommend it for a 30-year-old woman as opposed to a 60-year-old woman? RICHARD P. SAIK, MD, La Jolla, Calif: The authors have a unique sampling of 22 women who underwent mastectomy for minimal can¬ cer. I wonder if they reviewed the pathologic specimens to see if there were other foci of cancer or microinvasion in other areas of the breast. ARMANDO E. GIULIANO, MD, Los Angeles, Calif: Microinvasive cancer is invasive. The presentation would lead us to believe that intraductal and microinvasive are the same. Microinvasive cancer has shown that it has the ability to penetrate the basement membrane and metastasize. Along the spectrum of breast cancers, we know that the smaller the cancer, the less likely it is to have positive nodes. It is safe to assume that these are early lesions with a low incidence of positive nodes, but we should perform an axillary dissection. A negative axillary dissection is not an unnecessary procedure. It tells you whether there are lymph node métastases or not. It is not therapeutic, but then again, the removal of microscopically positive nodes may not be therapeutic. Are you really advocating that if a woman comes in with a palpable mass (as 17 of your patients did) and she has microinvasion, we do not perform an axillary dissection? Clare G. Peterson, MD, Portland, Ore: Invasive cancer is invasive cancer. I have spent my life in surgery regretting the lost opportunities to contain small malignancies by adequate en bloc operations. There should not be much confusion about the fact that microinvasion of breast cancer with breakthrough of the basement membrane is truly invasive infiltrating carcinoma of the breast with all the metastatic capabilities of such a lesion. The message of this report, demonstrating microinvasion (small, early, invasive cancers) treated by en bloc procedures (total mastec¬ tomy or modified radical mastectomy), shows excellent survival re¬ sults free of cancer at this time. This is vindication of the en bloc principle in the treatment of invasive breast cancer—the clinical arguments and dilemmas remain¬ ing being related to the true staging of the cancer before operation, and the extent and completeness of the en bloc resectional procedure carried out. I cannot agree with the categorical and contradictory statement that, "in this setting," axillary node dissection is unwarranted. Dr Morton: Our data clearly indicate that axillary lymph node métastases and recurrence are very rare in women who have microin¬ vasive intraductal carcinoma. Thus, if one can unequivocally make
such a diagnosis, axillary node dissection does not appear to be indicated. We agree that this conclusion must be regarded as prelimi¬ nary until more data are accumulated. We cannot be dogmatic when the total number of such patients is only 41. None of these patients had either lymph node métastases or recurrence after a 47-month median observation period, and it is unlikely that larger numbers or longer follow-up will change this conclusion. Nevertheless, we chal¬ lenge you to review your own experience with this entity and prove us wrong. One important question that our study does not answer nor at¬ tempt to answer relates to the multifocal nature of breast intraductal carcinoma and the frequency with which the initial biopsy results will be interpreted as microinvasive intraductal carcinoma, and, after subsequent mastectomy, other areas of frankly invasive intraductal carcinoma will be found with examination of the entire breast. Such patients would not have been included in our review because we were searching for cases of intraductal carcinoma with microinvasion only. Therefore, we must know how frequently pathologic examination of the entire mastectomy specimen leads to a modification of the initial
diagnosis.
Recurrence time is inversely proportional to the size of the lesion. That is, a smaller lesion may take longer to recur than a larger one. We need data from more centers and a longer follow-up before changing our routine treatment from a properly conducted procedure that treats the entire breast by mastectomy or a small procedure in which the entire breast is treated by radiation. This study never implies that the whole breast should not be treated. It only indicates that the patients with intraductal breast cancer and microinvasion have an excellent prognosis and a low incidence of axillary node métastases; all patients in this group except for one had treatment of the entire breast. Since we had up to 20 years of follow-up in some of our cases, I doubt if longer follow-up will change the basic conclusion. Dr Bodai, we do discuss all options for therapy with the patients and advise mastectomy or local resection and radiation. Age cannot be a primary consideration in terms of such discussions; the elderly woman is often as anxious to have breast preservation as a young woman.
Dr Saik, we did not get out the 177 cases and go through the breast by serial sections to look for additional areas of microinvasion. We
would not have included those cases in our review in which additional areas of frankly invasive carcinoma were found by the pathologists in the mastectomy specimens. Dr Peterson, it is important to point out that when no treatment failures occur, no benefit can be attributed to any treatment modal¬ ity. It does not support the en bloc principle, but rather, if anything, suggests the equivalent efficacy of "lesser procedures" in this patho¬
logic entity. Dr Giuliano, one has to either take the position that one will routinely perform an axillary dissection on every case such as this, or be committed to go back and do an axillary dissection if, on pathologic examination of the entire specimen, other areas of frank invasion are found. Until we know how frequently the diagnosis will be changed by examination of the entire specimen, it may be inappropriate to per¬ form an axillary dissection at the initial operation when this informa¬ tion may change the treatment plan.
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