Incidence of Lobular Carcinoma in Bilateral Breast Cancer
Terry Ft. Lewis, MD, Las Vegas, Nevada John Casey, MD, Lincoln, Nebraska Charles A. Buerk, MD, Las Vegas, Nevada Kirk V. Cammack, MD, Las Vegas, Nevada
Bilateral cancer occurs in 5 to 10 percent of all patients with breast cancer. Many studies have been initiated to define those patients at highest risk for development of cancer in the second breast based on the premise that early detection and treatment will improve prognosis. Suggested predictors of increased risk of bilateral breast cancer have been age, family history, and the presence of lobular carcinoma. Most researchers [I-5] have examined patients with lobular carcinoma in situ and have determined the rate of bilaterality for this group. In the present study, a set of patients with bilateral breast cancer was chosen to examine the incidence of lobular carcinoma in this subgroup of patients who are part of the spectrum of patients with bilateral breast cancer. Patients who are diagnosed as having lobular carcinoma are at greater risk of developing bilateral breast cancer and at an earlier age than are patients with nonlobular carcinoma. Material
The combined tumor registry of three community hospitals in a metropolitan area of 175,000 persons was reviewed. This registry included breast cancers diagnosed between the years 1963 and 1979. Clinical records and histologic slides were obtained for all patients with bilateral disease. Only patients for whom records and slides of both breast tumors were available were included in this study. ,411tissue slides from biopsy and mastectomy specimens were reviewed by the staff pathologist without his know.edge of the diagnosis assigned at the time of initial presentation. Light microscopic examination established diagnosis as either lobular (invasive or in situ) or ductal I:invasive or in situ). Specifically, criteria for diagnosis of lobular carcinoma in situ included greatly enlarged lobules, From Southern Nevada Memorial Hospital and University of Nevada Medical School, Las Vegas, Nevada. Requests for reprints should be addressed to Terry R. Lewis, MD, Department of Surgery, Southern Nevada Memorial Hospital, 2040 West Charleston. #502, Las Vegas, Nevada 89102. Presented at the 34th Annual Meeting of the Southwestern Surgical C:ongress, Coronado, California, April 26-29, 1982.
Volume 144, December
increased cellularity with uniform, closely packed cells, round nuclei with few mitoses, scanty cytoplasm, absence of necrosis, and possible extralobular ductal involvement. Invasive lobular carcinoma is characterized by haphazard cell growth, dense stroma, the absence of gland formation, and small cells in Indian file. The pattern is targetoid around non-neoplastic ducts. Multiple diagnoses from a single breast were possible, but in situ diagnosis was made only if no invasive element was seen. Tumor size, nodal status, and histologic evidence of metastatic disease were recorded based on slide review. Age and timing of diagnosis were obtained from clinical records. Results
The tumor registry recorded 1,865 patients with breast cancer during a 16 year period. Bilateral disease occurred in 105 patients (5.6 percent). Complete records and slides were available in 52 cases and they comprise the study group. Invasive ductal carcinoma was the most common diagnosis, occurring in 89 of the 104 breasts (85.6 percent). Ductal carcinoma in situ without invasion occurred in nine (8.7 percent) and medullary carcinoma in three (2.9 percent). Lobular carcinoma occurred in 23 of the 104 breasts (22 percent). Lobular carcinoma in situ occurred in 4 (3.8 percent) and invasive lobular carcinoma in 19 (18.3 percent). Lobular carcinoma was found with ductal carcinoma in 12 breasts (11.5 percent of the breasts). Nineteen patients with lobular carcinoma in at least one breast had a mean age of 57.3 years at the time of first diagnosis, and 61.1 years at the time of the second diagnosis: an interval of 45.3 months. The average age of 33 patients with nonlobular carcinomas was 61 years at the time of first diagnosis and 64.8 years at the time of second diagnosis: an interval of 40.2 months. The total study group of 52 patients with bilateral carcinoma of the breast averaged 59.6 years at the time of first diagnosis and 63.4 years at the time of second diagnosis: an interval of 42 months.
Lewis et al
In analyzing the time of diagnoses in patients with bilateral breast cancer, intervals between histologic diagnoses of less than 3 months were considered to indicate simultaneous or synchronous onset of disease. Of the 52 patients, 17 (32.7 percent) had simultaneous onset. In 20 (38.5 percent) patients disease was first noted in the right breast and in 15 (28.8 percent) patients it was first noted in the left breast. When the subsets of patients with lobular and nonlobular carcinoma were compared, 8 of 19 (42 percent) of the patients with lobular carcinoma in at least one breast had simultaneous onset of disease compared with 9 of 33 (27 percent) in the nonlobular group. In the 35 patients in whom bilaterality was not simultaneous, tumor size was 2.6 cm in the first breast diagnosed and 1.3 cm in the second; the percentage of positive nodes was 31.4 percent in the first breast and 34.3 percent in the second breast. Comments The multicentric nature and tendency toward bilateral occurrence of breast carcinoma has been well documented. Reports vary as to the extent and timing of this phenomenon. In 1977 Urban  retrospectively reviewed 455 patients whose breast cancers were treated by radical mastectomy more than 10 years previously. He found that in 9 percent of the patients clinically apparent disease developed in the remaining breast. Based on this finding, 954 patients were subjected to simultaneous biopsy of the opposite breast, and bilateral disease was demonstrated in 12.5 percent; the majority at an in situ or noninvasive stage. In patients with lobular carcinoma in situ there is an even greater probability of development of bilateral disease. Reports on the occurrence of bilateral lobular carcinoma in situ range from 13 to 47 percent [l--5]. The wide range is explained partly by length of follow-up, criteria for diagnosis, and how vigorously the lesion is searched for. In studies where contralateral biopsy was used, greater rates of bilaterality were reported. Donegan and Perez-Mesa  performed biopsies of the opposite breast in 36 patients with lobular carcinoma, in situ or invasive, and found bilateral cancers in 30.6 percent of those studied. Herein, we approach the problem from a different perspective. The histologies of known bilateral carcinomas were examined. Lobular carcinoma in situ comprises 3 to 6 percent of all breast cancers and invasive lobular carcinoma approximately 5 percent of all breast cancers. In the present study, 36 percent of those with bilateral carcinoma had lobular carcinoma in at least one breast, and 7.7 percent had lobular carcinomas in both breasts. This finding is in agreement with another study reported by Beahrs et al , in which 41 percent of 29 bilateral breast cancers were lobular carcinomas.
Lattes and Rosen [g-11] have suggested that detection of lobular carcinoma in one breast, particularly when it is in situ, should be considered a marker of possible disease in the other breast. Their suggestion is based on studies showing equal risk for either breast when biopsy-proved lobular carcinoma in situ is followed clinically. Lobular carcinomas were detected in 22 percent of the breasts we examined, and in half they were detected in conjunction with ductal carcinomas. In the present study of 11 patients with lobular carcinoma, 4 had lobular carcinoma in the first breast that was diagnosed but not in the second, and 5 had lobular carcinoma in the second breast diagnosed but not in the first. Two patients had lobular carcinoma only in each breast. Therefore, in half of these patients the significance of lobular disease as a marker was not useful since it was not diagnosed in the first breast. It is important to remember that although the detection of lobular carcinoma should raise suspicion of bilateral disease, in the majority of cases of bilateral disease it will be ductal. The distribution of breast cancers by age at diagnosis is described by a typical bell shaped curve, with a peak at 60 to 70 years of age. The curve for patients with bilateral disease is shifted slightly to the left but has a blunted peak at 40 to 60 years of age. The subset of patients with bilateral,. lobular disease is compared with those with nonlobular bilateral disease in Figure 1. Bilateral lobular carcinoma occurs at all ages but first diagnosis tends to occur at a younger age than it does in those with nonlobular bilateral disease. The interval between first and second diagnoses in this group of patients ranged from simultaneous occurrence to more than 20 years. Discovery of cancer in both breasts at the same time was more likely in the group of patients with lobular carcinoma. However, as seen in Figure 2, by 2 years the cumulative number of patients with manifestations of bilateral disease was similar in those with lobular carcinoma and those with other types of carcinoma. This suggests that if the advantage to early detection of cancer in the second breast in those with lobular cancer is to be realized, bilaterality should be diagnosed at the time of first diagnosis. Further support for early treatment of the second breast is obtained by studying tumor size in the group in whom occurrence was not simultaneous. The mean tumor size in the second breast was half of that in the first, but there was no difference in the number of positive nodes. This finding is in agreement with the report of Donegan et al [ 71 of second tumors discovered by clinical examination. Second tumors were 1 cm smaller and were more often clinically localized, but there was no reduction in the rate of axillary metastases. This study supports the validity of biopsy of the contralateral breast when lobular carcinoma is dis-
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Lobular Carcinoma in Breast Cancer
Figure 1. Age comparison. Decade of aga at time of first diagnosis in patients with and without lobular carcinoma.
covered. The amount of breast tissue to be removed with biopsy and the role of prophylactic mastectomy will require further study and longer follow-up. It is hoped that further development of community tumor registries such as the one from which this data was generated will aid in answering these questions.
Those with lobular cancer tended to he younger and more likely to have simultaneous cancers than did patients with nonlobular carcinoma. In those patients in whom the occurrence of tumors was not simultaneous, they were smaller in the second breast but had similar rates of axillary metastases. This study raises the question of how best to manage the contralateral breast in patients with breast cancer. Lobular carcinoma is one marker of the likelihood for development of disease in the second breast; but, if advantage is to be gained by this finding, investigation of the opposite breast is best done early. Finally, thorough examination of patients with nonlobular carcinoma must not be ignored because they still comprise the majority of bilateral breast cancers.
Summary The histology and clinical records of 52 patients with bilateral breast cancer recorded in a community tumor registry were reviewed. Previous studies have demonstrated the propensity of lobular carcinoma to occur bilateraly. This view is supported by the large number of lobular cancers found in our patients. Thirty-six percent. of the patients with bilateral disease had lobular cancer in at least one breast.
Figure 2. Interval between diagnosis of lobular and nonlobular patients. Cumutat&e percentage of patients with and without lobular carcinoma who had manifestation of bffateral disease with time. Zero time represents simultaneous bilateral disease.
Lewis et al
References 1. Fisher ER, Fisher 8. Lobular carcinoma of the breast. Ann Surg 1977;185:377-85. 2. Hutter RVP, Foote FW Jr. Lobular carcinoma in situ. Long-term follow-up. Cancer 1969; 24:1081-5. 3. Lewison EF, Finny GG Jr. Lobular carcinoma in situ of the breast. Surg Gynecol Obstet 1968; 126: 1280-6. 4. Snyder RE. Mammography and lobular carcinoma in situ. Surg Gynecol Obstet 1966; 122:255-60. 5. Urban JA. Bilaterality of cancer of the breast. Biopsy of the opposite breast. Cancer 1967;20:1867-70. 6. Urban JA, Papachristou D, Taylor J. Bilateral breast cancer. Biopsy of the opposite breast. Cancer 1977;40:1968-73. 7. Donegan WL, Perez-Mesa CM. Lobular carcinoma-an indication for elective biopsy of the second breast. Ann Surg 1971;176:178-87. 8. Report of Working Group to Review BCDDP. Pathology review of minimal breast cancers detected in BCDDP. J Nat1Cancer lnst 1979;62:673-9. 9. Lattes R. Lobular neoplasia (lobular carcinoma in situ) of the breast. A histological entity of controversial clinical significance. Pathol Res Pratt 1980;166:415-29. 10. Rosen PP. Lieberman PH, Braun DW, Kosloff C, Adair F. Lobular carcinoma in situ of the breast. Am J Surg Pathol 1979;2: 225-51. 11. Rosen PP. Lobular carcinoma in situ: recent clinicopathologic studies at Memorial Hospital. Pathol Res Pratt 1980;166: 430-55.
Discussion Richard I. MacArthur (Kansas City, KS): Dr. Lewis has reminded us of the necessity for increased vigilance in monitoring the remaining breast in patients who have carcinoma of the breast. He has also made the important point that there is an increased incidence of bilateral cancer in patients with lobular carcinoma, and that often the tumor in the second breast is not lobular cancer but, rather, a ductal carcinoma. At the University of Kansas, we have routinely used both preoperative mammography and computerized tomography of the breast when evaluating our patients with primary breast cancer. We have not used routine biopsy on the opposite breast in the last 4 years. We believe that using mammography and the CAT scan allow us to select the patients who should have contralateral biopsy.
I would Iike to ask Dr. Lewis to recommend how to manage the second breast in patients with carcinoma? Is mammography adequate, or should we proceed with mirror image biopsy? Finally, does he have any experience using the CAT scan for finding disease in the opposite breast? Claude H. Organ, Jr. (Omaha, NE): My concern with this paper involves facts about nonlobular carcinoma of the breast. As many of you know, we have long had interest in the genetics of breast cancer. I would support the concept that taking a family history is cost effective, simple, and may be very revealing. Some of the characteristics that Dr. Lewis has expressed are common characteristics of familial breast cancer; for instance, a high incidence of bilaterality and young age at onset. Two points need to be made: First, when these patients are followed for a long period of time, an associated heterogeneity is often observed that is quite interesting and relates to carcinoma of the colon and carcinoma of the uterine fundus. Second, they have an improved survival of about 18 percent in those with carcinoma of the breast and about 15 percent improved survival (5 years disease-free) in those with carcinoma of the colon. Terry R. Lewis (closing): I agree that there is much controversy concerning therapy of the opposite breast in the patient with breast cancer. With regard to mammographic and CAT scan examinations, I think the mammogram is an integral part of follow-up. I have no clinical experience with the CAT scan. I think you have to view lobular carcinoma as another predictor of bilaterality in determining the type of therapy needed in addition to age and, as Dr. Organ has mentioned, family history. These factors have to be weighed by the surgeon when deciding how aggressively to approach the opposite breast. I believe that a contralateral biopsy involving 20 to 25 percent of the breast parenchyma may be the most prudent course in high-risk patients. Other factors, such as patient anxiety or the desire for reconstruction may even provide a role for prophylactic mastectomy on the opposite side. If we elect to follow patients with lobular cancer we must realize the risks and share the responsibility for the increased risk of development of cancer in the opposite breast.
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