Histologic Comparison of Mammary Carcinomas among a Population of Southwestern American Indian, Spanish American, and Anglo Women WILLIAM C. BLACK, M.D., GERALD M. BORDIN, M.D., ELIZABETH W. VARSA, M.D., AND DORIS HERMAN, M.D.

AGE-ADJUSTED MORTALITY RATES for carcinoma of the female breast have been determined for numerous areas throughout the world. Utilizing ageadjusted mortality rates, populations at high, low, and intermediate risk have been identified. For example, Japanese women who remain in their own country have one of the lowest age-standardized incidence rates in the world for mammary carcinoma. 2 ' 3,9 Interesting comparisons of survival rate, histologic tumor type, growth pattern, and inflammatory reaction have been reported for low-risk (Japanese women) and high-risk (American women) groups. l ' 5,6,810 Within the population served by the New Mexico Tumor Registry the relative incidence of carcinoma of the breast is distinctly lower among American Indian than among Anglo women with corresponding ageadjusted incidence rates per 100,000 population of 26.3 and 86.7, respectively. 7 Spanish American women demonstrate an intermediate incidence of 40.5 per 100,000.7 Because histologic differences between mammary carcinomas have been described between international high-and low-risk groups, we became interested in comparing the histologic characteristics of mammary Received January 12, 1978; received revised manuscript and accepted for publication April 6, 1978. Supported in part by the N.I.H. Grant No. Nol-CN-65173. Address reprint requests to Dr. Black: Cancer Research and Treatment Center, University of New Mexico, 900 Camino De Salud, N. E., Albuquerque, New Mexico, 87131.

Department of Pathology, and University of New School of Medicine, University of New Mexico Research and Treatment Albuquerque, New

carcinoma within these three ethnic groups (American Indians, Spanish Americans, Anglos) have differing age-adjusted incidence rates and residing in the same geographic region. We specifically wondered whether histologic features of mammary carcinoma in American Indians might be similar to those described for Japanese women, since both are at low risk for the development of carcinoma of the breast. Materials and Methods The New Mexico Tumor Registry has accessioned only 71 Indian women with histologically confirmed carcinoma of the breast occurring between 1965 and 1976. Of the 71 cases, 45 had adequate histologic and clinical documentation of their tumors for inclusion in this study. Because American Indians comprise a smaller proportion of the population at risk within New Mexico and have the lowest age-adjusted incidence rate, the smallest number of breast carcinomas available for study came from this ethnic group. Thus, the 45 Indian patients were designated as the index group. Clinical information and histologic material pertaining to these 45 tumors was obtained from three New Mexico hospitals: the Gallup Indian Medical Center, in Gallup, the Lovelace-Bataan Medical Center, and the Bernalillo County Medical Center (formerly the Bernalillo County Indian Hospital), both in Albuquerque. Comparable clinical data and histologic materials were obtained for 45 Anglo women and 45 Spanish American women with mammary cancer, matched for age and for year of diagnosis. These cases were obtained through random selection from the pathology files of the Lovelace-Bataan Medical Center and Bernalillo County Medical Center. Three pathologists independently studied representative sections of the primary tumor to evaluate the nature of its interface with surrounding mammary parenchyma (circumscribed

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Mexico Cancer Center, Mexico

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Black, William C , Bordin, Gerald M., Varsa, Elizabeth W., and Herman, Doris: Histologic comparison of mammary carcinomas among a population of Southwestern American Indian, Spanish American, and Anglo women. Am J Clin Pathol 71: 142-145,1979. Primary carcinomas of the breast were studied in age-matched populations of Southwestern American Indian, Spanish American, and Anglo women from an area served by the New Mexico Tumor Registry. Histologic tumor type, nuclear grade, and stromal inflammatory response were compared among these three groups. Indian women presented with less favorable tumor stage at diagnosis. Histologic tumor types were similar with the exception that lobular carcinoma was less frequent among Indian and Spanish American than among Anglo women. Carcinomas from Indian patients showed less differentiated nuclei than those from the other groups. (Key words: Carcinoma of the breast; Ethnic differences.)

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ETHNIC DIFFERENCES IN MAMMARY CARCINOMA

or irregular), and each of the 135 tumors was also classified for histologic type, nuclear grade, stromal inflammatory response, and presence or absence of an intraductal component. Tumor stage at diagnosis was recorded for each patient, including the greatest diameter of the primary lesion and the presence or absence of skin ulceration, fixation to chest wall or skin, and clinical evidence of inflammatory carcinoma. Basic criteria for assignment of histologic type, degree of circumscription, nuclear grade, and stromal cellular reaction to the tumor were as outlined in The Pathology of Invasive Breast Carcinoma; A Syllabus Derived from Findings of the National Surgical Adjuvant Breast Project (Protocol Number 4). 4 Results

The principal tumor pattern in each group was infiltrating ductal carcinoma (Table 1). In four patients (one Indian, one Spanish American, and two Anglo) a diffusely infiltrative neoplasm was characterized by small cells with scanty cytoplasm invading as individually small clusters of tumor cells, single tumor cells, or cells arranged in thin cords with no tubular differentiation. This pattern is generally accepted as representative of invasive lobular carcinoma, but in these four patients there was also extensive intraductal carcinoma within the substance of the primary tumor, while at the margins no intralobular carcinoma was present. Three additional carcinomas from Anglo women displayed a typical invasive lobular carcinoma pattern without intraductal carcinoma, and in two of the three lobular carcinoma in situ was noted as well. A pattern other than invasive ductal carcinoma was found in one Indian patient with an infiltrating papillary carcinoma and in one Spanish American woman with infiltrating mucinous carcinoma (Table 1). Tumor

Configuration/Circumscription

All carcinomas were separated into one of two categories. The first was designated as "irregular" or "stelTable I. Tumor Types among Ethnic Groups Dominant Tumor Type Infiltrating ductal carcinoma Infiltrating lobular carcinoma with intraductal carcinoma Infiltrating papillary carcinoma Mucinous carcinoma Infiltrating lobular carcinoma TOTAL

American Indian

Spanish American

Anglo

43

43

40

1

1

2

1 0 0

0 1 0

0 0 3

45

45

45

Table 2. Ethnic Groups and Nuclear Grades Nuclear Grade I Ethnic Group American Indian Spanish American Anglo American

II

III

Total

(Number of Patients) 28 16 16

17 27 25

0 2 4

45 45 45

late" on the basis of scanning-lens examination of the tumor margins and their relationship to surrounding mammary parenchyma. These lesions displayed an irregular, ragged infiltrative border. The second category was designated as "circumscribed," indicating a blunt, pushing interface with surrounding parenchyma at the margins. Thirty-six of 45 carcinomas from Indian patients demonstrated the irregular, stellate pattern, as did the tumors from 39 Spanish American and 36 Anglo patients. Nuclear Grade Tumor nuclei were separated into three groups on the basis of degree of differentiation. Grading observations included pleomorphism and hyperchromatism, relative prominence of nucleoli, and frequency of mitotic figures, both normal and abnormal. Tumors with the least differentiated nuclei were categorized as grade 1 and those with the best nuclear differentiation as grade 3. Table 2 shows the relationships between ethnic group and nuclear grade. Cellular Reaction to Tumor (Inflammatory

Response)

Three grading categories were utilized: absent-tonegligible, slight-to-moderate, and moderate-to-marked. Of the 45 carcinomas from American Indian women, 19 displayed absent or negligible cellular response, and 26, slight-to-moderate response (lymphocytes and plasmacytes). Of the 45 carcinomas from Spanish American patients, 30 demonstrated absent or negligible response, 14, a slight-to-moderate response, and in one tumor there was an extensive round-cell infiltration. Of 45 carcinomas from Anglo women, 28 showed an absent or negligible response, 16, a slight-to-moderate reaction, and one, an intense lymphocytic and histiocytic response. Intraductal Tumor

Component

Intraductal carcinoma was present within the substance of or at the margin of the tumors in 23 Indian women, 23 Spanish American women, and 31 Anglo women.

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Histologic type

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BLACK ETAL.

Table 3. Tumor Diameters and Ethnic Groups Tumor Diameter Ethnic Group

4 cm (No.)

Total No.

American Indian Spanish American Anglo

5 8 13

18 21 22

20 13 7

43 42 42

Table 4. Distribution of All Patients by Age Number of Patients

20-29 30-39 40-49 50-59 60-69 70-79 80-84

3 7 10 12 7 5 1

Tumor Stage at Diagnosis The greatest diameter of the primary carcinoma for each of the three ethnic groups is shown in Table 3. Two tumors from the Indian group and three each from the Spanish American and Anglo groups could not be evaluated in this regard because of insufficient information in the chart of pathology report. Among Indian patients, seven presented with ulcerated carcinomas with or without fixation to the chest wall and four with fixation to the skin or chest wall in the absence of ulceration; three presented the clinical signs of inflammatory carcinoma with neither tumor fixation nor ulceration. Thus 14 of 45 Indian patients displayed unfavorable physicalfindingsapart from or in addition to large tumor size at diagnosis. Similar unfavorable physical findings were noted in nine Spanish American patients and five Anglo patients. Age distribution for each group is shown in Table 4. Discussion When comparing the histologic appearance of mammary carcinomas from distinctive risk groups, one will find significant differences if variations in histologic patterns occur with great frequency or if large numbers of patients are evaluated statistically to detect histologic differences of lesser degree. This study, based on the comparison of mammary carcinomas in three groups composed of only 45 individuals each is thus capable of detecting only gross variations in histologic pattern. Previously reported comparisons of tumor types of American and Japanese women have shown an increased frequency of intraductal carcinoma, medullary carcinoma, and mucinous carcinoma among Japanese

patients.5,6,8,10 We found nothing to suggest an increased prevalence of any of these forms of carcinoma among the Indian or Spanish American patients, as compared with the Anglo group. We found that for Indian, Spanish American, and Anglo women infiltrating ductal carcinoma is by far the most common histologic type, and neither intraductal nor medullary carcinomas were found among the 135 tumors studied. Our findings suggest that lobular carcinoma may occur less frequently in Indian and Spanish American women, as compared with age-matched Anglo women. Interestingly, the incidence of lobular carcinoma, whether in situ or invasive, appears to be less in Japan than in America.1,8 We did not detect an unusual prevalence of minor or additional histologic subtypes of mammary carcinoma in any ethnic group either in the nature of the subtype or in frequency, as compared with data from the National Surgical Adjuvant Breast Project.4 Circumscribed infiltrating ductal carcinomas were detected more commonly among Japanese women than among American women, but we found no differences in this regard among the three ethnic groups studied.58 Our data suggest that the average degree of nuclear differentiation may be less in carcinomas from American Indian patients, as compared with those from other groups. Nuclear grade is, to an extent, a subjective evaluation, and we find it difficult to compare our observations with those from other studies.1'4 However, within our own groups, carcinomas from Indian women showed a much higher frequency of lesions with "anaplastic" nuclei than those from Spanish American or Anglo women, and no examples of carcinomas with a well-differentiated nuclear structure were found in the Indian group. While an intense stromal leukocytic infiltrate was found in only two of 135 tumors, a slight to moderate degree of stromal reaction appeared to be more prevalent in carcinomas from the American Indian patients. (We specifically excluded inflammatory responses in the region of ulcers or previous biopsy wounds.) Increased prominence of lymphoid stroma has been noted in breast carcinomas from Japanese women.1*6,8 Tumors from Anglo patients displayed a greater frequency of intraductal carcinoma than those from the other groups (72 versus 51%). Foci of intraductal carcinoma are perhaps more likely to be found around smaller carcinomas where there is less replacement and/or better sampling of the surrounding neoplastic tissues in routine sections. Since the carcinomas in Spanish American and Indian patients tended to be larger than those in Anglos, we suspect that the increased prevalence of intraductal carcinoma in Anglos was a function of tissue sampling around the perimeter of smaller neoplasms.

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Age (Yr)

A.J.C.P. • February 1979

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ETHNIC DIFFERENCES IN MAMMARY CARCINOMA

In conclusion, this study does not demonstrate clearly defined differences in the incidence of specific histologic types of mammary carcinoma among women from three ethnic groups residing in this geographic region. The only apparent exception is an underrepresentation of lobular carcinoma among Spanish American and American Indian women. Additionally, it is very uncommon

for carcinoma to be found in its preinvasive or intraductal phase at the time of initial biopsy in Indian women, and this observation no doubt reflects the fact that Indian patients, as a group, present with advanced stage of disease in comparison with women from the other ethnic groups. References 1. Chabon A, Takeuchi S, Sommers S: Histological differences in breast carcinoma of Japanese and American women. Cancer 33:1577-1579, 1974 2. Correa P: The epidemiology of cancer of the breast. Am J Clin Pathol 64:720-727, 1975 3. Doll R, Muir C, Waterhous J (eds): Cancer Incidence in Five Continents. Volume II. New York, Springer-Verlag, 1970 4. Fisher E. Gregorio R, Fisher B: The pathology of invasive breast cancer: A syllabus derived from findings of the National Surgical Adjuvant Breast Project (Protocol No. 4). Cancer 36:1-84, 1975 5. MacMahon B, Morrison A, Ackerman L, et al: Histologic characteristics of breast cancer in Boston and Tokyo. Int J Cancer 11:337-344, 1973 6. Morrison A, Black M, Lowe C, et al: Some international differences in histology and survival in breast cancer. Int J Cancer 11:261-267, 1973 7. New Mexico Tumor Registry, Cancer in New Mexico 1969— 1972: 53, 1975, Albuquerque, New Mexico 8. Rosen P, Ashikari R, Thaler H, et al: A comparative study of some pathologic features of mammary carcinoma in Tokyo, Japan, and New York, USA. Cancer 39:429-434, 1977 9. Seidman H: Cancer of the breast: Statistical and epidemiological data. Cancer 24:1355-1378, 1969 10. Wynder E, Kagitani T, Kuno J, et al: A comparison of survival rates between American and Japanese patients with breast cancer. Surg Gynecol Obstet 117:196-200, 1963

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There is little question that Indian patients present with more advanced tumor stage at diagnosis. Only 17 of 45 Indian women (37.8%) had primary tumors measuring less than 5 cm in diameter at the time of diagnosis or were free of "dire signs" such as fixation of the primary tumor to the skin or chest wall, ulceration of overlying skin, or clinical evidence of inflammatory carcinoma. We did not attempt to specifically evaluate axillary status, but it was evident that unfavorable physical findings pertaining to the primary tumor often correlated with clinically advanced axillary metastases. The New Mexico Tumor Registry has accumulated data supporting ourfindingsregarding stage at diagnosis from a much larger patient population. Among 1,822 women with carcinoma of the breast, the incidence of preinvasive or in situ carcinoma for Anglo women is 5.9% and for Spanish American women, 2.8%; there are no cases of in situ carcinoma recorded for American Indian women. Remote metastases were found in 10.2% of Anglo women at the time of diagnosis, in 12.5% of Spanish American women, and in 25.8% of American Indian women.

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Histologic comparison of mammary carcinomas among a population of Southwestern American Indian, Spanish American, and Anglo women.

Histologic Comparison of Mammary Carcinomas among a Population of Southwestern American Indian, Spanish American, and Anglo Women WILLIAM C. BLACK, M...
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