Carcinoma of the Breast in Young Women Gordon F. Schwartz,
MD, Philadelphia,
John V. Zeok, MD,* Philadelphia,
Pennsylvania
Pennsylvania
The optimal primary treatment for mammary carcinoma is a subject of contemporary controversy, with staunch and knowledgeable advocates of widely disparate modes of therapy. For the physician who encounters an unfortunate young woman with breast cancer, this controversy becomes even more frustrating, because of even wider variations in survival reported for these patients, regardless of the therapy chosen. Opinions concerning the relative virulence of breast carcinoma in young women aged thirty years or younger differ markedly. Some regard breast cancer in this age group no different from that disease in older women [I-6], whereas others consider breast cancer in these young women more frequently and/or more rapidly fatal [ 71. Although several contemporary authors have concluded that these young women are not necessarily doomed, Kleinfeld, Haagensen, that relative youth and Cooley [7] h ave commented affects prognosis almost as much as the status of the axillary lymph nodes, and their data imply a poor prognosis in these women. More recently, Haagensen [B] has noted survival in women less than thirty years old only when the disease was noted in its earliest stage, Stage A, and even in these women, ten year survival was only 51 per cent, as compared with more than 70 per cent survival in women of all ages with Stage A cancers treated by radical mastectomy. Part of the controversy regarding optimal treatment for young women with breast cancer must relate to the relatively infrequent occurrence of the disease in this age group, representing less than 2 per cent of all mammary carcinomas. Except for the series of women thirty-five years and younger reported by Treves and Holleb [5], all of the reported series discuss only small numbers of patients, thus making valid statistical observations difficult to achieve. Additionally, there is little mention in the literature of the clinical stage of disease at the time these young
From the Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania. This work was supported in part by a clinica~fellowshipirom the American Cancer Society (JVZ). Reprint requests should be addressed to Gordon F. Schwartz. MD, Department of Surgery, Jefferson Medical College, 1025 Walnut Street, Philadelphia, Pennsylvania 19107. ’ Formerly Chief Resident in Surgery and Clinical Fellow of the American Cancer Society.
570
women received their primary therapy. The necessity for accurate clinical staging of mammary carcinoma to compare different methods of treatment in different groups of patients has been emphasized in the literature [9]. Because the total number of young women with breast cancer has been small, there have been few attempts at further subdivision of this already small number into even smaller subgroups based on clinical stage of disease and/or lymph node status. Material
and Methods
In 1951, the Philadelphia County Medical Society organized a breast cancer registry as part of an attempt to reduce delay in the diagnosis and treatment of mammary carcinoma. During the period of its operation, 1951 through 1964, the registry recorded 9,003 patients [IO]. It has been estimated previously that these records include 85 to 90 per cent of all breast cancers encountered in Philadelphia during this period of time [IO]. This registry was culled and charts were reviewed for all patients thirty years of age and younger who were encountered between the inception of the program in 1951 and December 31, 1963. The age of record was the patient’s age at time of initial definitive therapy; thus, if a patient had had symptoms in her thirtieth year but was treated after her thirty-first birthday, she was not included in the study group. Similarly, primary therapy must have been initiated prior to January 1,1964, to insure a minimal follow-up period of ten years, since five year survival data are considered inconclusive in the evaluation of patients with mammary carcinoma [8]. Review of the Philadelphia County Medical Society breast cancer registry yielded the records of 111 patients thirty years or younger with histologically documented carcinoma of the breast for whom ten year follow-up was complete. Several additional patients encountered during the same time period but lost to follow-up, were not included in the study. Hospital records were reviewed, and the clinical data available were used to classify all patients into one of four clinical stages according to the Columbia Clinical Classification, based on Haagensen’s criteria, which are reiterated in Table I [9]. If the clinical data were insufficient to enable staging according to the Columbia Classification, the lesion was designated as “unspecified clinical classification” and tallied as such. Scrutiny of the pathology reports of each patient allowed further subdivision within each clinical stage into those patients with negative axillary lymph nodes and those patients whose
The American Journal ol Surgery
Breast Cancer in Young Women
TABLE I
Columbia Clinical Classification [91
Stage
No skin edema, ulceration, or solid fixation of tumor to chest wall. Axillaty nodes not clinically involved. Stage B: No skin edema, ulceration, or solid fixation of tumor to chest wall. Clinically involved axillary nodes-but less than 2.5 cm in transverse diameter and not fixed to overlying skin or deeper structures of axilla. Stage C: Any one of the five grave signs of advanced breast carcinoma: 1. Edema of skin of limited extent (involving less than one third of the skin over the breast). 2. Skin ulceration. 3. Solid fixation of tumor to chest wall. 4. Massive involvement of axillary lymph nodes: a. A single node, or group of fused nodes, measuring 2.5 cm or more in transverse diameter. b. A chain of nodes extending high into the axilla. 5. Fixation of the axillary nodes to overlying skin or deeper structures of axilla. Stage 0: All other patients with more advanced breast carcinoma, including: 1. A combination of any two or more of the five grave signs listed above in Stage C. 2. Extensive edema of skin (involving more than one third of the skin over the breast). 3. Satellite skin nodules. 4. The inflammatory type of carcinoma. 5. Clinically involved supraclavicular lymph nodes. 6. Internal mammary metastases as evidenced by a parasternal tumor. 7. Edema of the arm. 8. Distant metastases. A:
lymph nodes contained foci of metastatic carcinoma. Patients not undergoing radical mastectomy or whose pathology records did not note the status of the axillary nodes were recorded as “axillary nodes unspeci-
axillary
fied.” Survival data were thus obtained for patients in all four clinical stages with and without axillary node metastases.
Results Tabulation of the results of this study are summarized in Tables II and III. Of the 111 patients followed for at least ten years, 66 (59.5 per cent) were classified as Stage A, 21 (18.9 per cent) as Stage B, 10 (9.0 per cent) as Stage C, and 7 (6.3 per cent) as Stage D; 7 patients (6.3 per cent) were unable to be classified clinically from the available data and were therefore listed as “unspecified clinical classification.” Thus, a majority of these young women, 87 (78.4 per cent), had what would be considered generally as early or not locally advanced mammary carcinoma, that is, Stage A or B. With regard to treatment, almost all patients in Stages A, B, and C underwent radical mastectomy. One patient with Stage A disease had a modified radical mastectomy, and one patient with Stage C disease had a simple mastectomy, followed by oophorectomy and adrenalectomy as her primary definitive treatment. Most of the Stage D patients did not undergo radical mastectomy because of the known extent of their disease. Postoperative irradiation was administered to many of the patients with Stage A, B, and C carcinomas. Several patients
v-
131, May 1976
in these stages were also subjected to prophylactic surgical castration as part of their initial definitive treatment. The status of axillary lymph nodes in the patients subjected to radical mastectomy is noted in Table II. Of the sixty-six patients with Stage A carcinoma, 40.9 per cent had negative lymph nodes and 39.4 per cent had at least one axillary lymph node containing metastatic carcinoma. The remainder had no mention made of the lymph node status in the pathology report, or the data were unretrievable. Of the patients with Stage B mammary carcinoma, 9.5 per cent had no axillary lymph node involvement, 85 per cent had at least one positive lymph node, and 4.5 per cent were unspecified as to lymph node status. Only one patient with Stage C disease (10 per cent) had no involved lymph nodes, although 40 per cent of this group had unspecified axillary involvement. Of the ten Stage C patients five (50 per cent) had at
TABLE II
Stage A 6 C
Incidence of Axillary Lymph Node Metastasis No Nodes Involved 27 (40.9%) 2 (9.5%) 1 (10.0%)
Nodes
Nodes
Involved
Unspecified
26 (39.4%) 18 (85.7%) 5 (50.0%)
13 (19.7%) 1 (4.8%) 4 (40.0%)
D” Unclassified* * Lymph node status unknown because axillary tion is rarely performed or data are incomplete.
dissec-
571
Schwartz and Zeok
TABLE I II
10 Year Survival Related to Clinical Stage of Disease and Axillary Node Metastasis Total Number of Patients
Number of Survivors
Stage A No Nodes involved Nodes Involved Nodes Unspecified Total Stage A
27
18 (66.7%)
26 13 66
2 (7.7%) 7 (53.8%) 27 (40.9%)
Stage B No Nodes Involved Nodes Involved Nodes Unspecified
2 18 1
0 6 (33.3%) 0
21
6 (28.6%)
1 5 4 10
1 (100%) 0 1 (25.0%) 2 (20.0%)
Total
Stage B
Stage C No Nodes Involved Nodes Involved Nodes Unspecified Total Stage C Total
Stage D*
Unclassified
by Stage*
that
0
7
2 (28.6%)
111
Grand Total * Indicates ascertained.
7
status of axillary
lymph
37 (33.3%) nodes was not
least one positive axillary lymph node. Of the patients with Stage D carcinoma, two underwent radical mastectomy and both had many involved lymph nodes in their axillae. Survival data according to stage of disease are recorded in Tables III. Survival for all patients in Stages A through D were 40.9,28.6,20, and 0 per cent, respectively. When patients were subdivided by lymph node status, nineteen of the thirty patients without lymph node metastases (63.3 per cent) survived, regardless of the clinical stage of disease. However, of the forty-nine patients with involved axillary lymph nodes, only eight (16.3 per cent) survived, regardless of stage of disease, even though a majority of the forty-nine patients were in Stages A and B. The ten year survival for patients with Stage A carcinoma without axillary lymph node metastases was 66.6 per cent, but of the twenty-six patients with Stage A carcinoma with axillary lymph node metastases, only two patients (7.7 per cent) were alive at the end of ten years. Of the entire group of 111 patients, 37 (33.3 per cent) were alive ten years after primary therapy for their breast carcinoma.
Comments
Excepting the large series reported by Treves and Holleb [5] on patients thirty-five years of age and
572
younger, this group of 111 patients, all aged thirty years or younger, represents the largest group of patients in this age group, clinically classified as to stage of disease when initially treated and subsequently followed for at least ten years. The survival data presented herein vary considerably from most other reported studies except for those patients reported by Haagensen [8], who reported fifty-nine patients less than thirty years old encountered at the Columbia-Presbyterian Medical Center between 1912 and 1960. Their overall ten year survival was 30 per cent, with 51 per cent of the patients with Stage A carcinomas surviving ten years after radical mastectomy. Paralleling our own experience, fourteen of twenty-two Haagensen’s Stage A patients (63.6 per cent) without axillary metastases survived ten years after radical mastectomy, whereas only two of nine patients (22.2 per cent) with axillary metastases, despite their Stage A clinical classification, survived ten years. Reviewing the results of treatment of breast carcinoma in these women aged thirty years and younger, we noted several points. With the exception of one patient who underwent modified radical mastectomy, the only patients who survived ten years were treated by radical mastectomy. Secondly, of the eight patients who survived ten years despite the presence of positive axillary lymph nodes, only one patient had a primary lesion larger than 3.0 cm in diameter, and four of these eight surviving patients had lesions 2.0 cm or smaller in diameter. Criticisms common to most reports of younger women with breast carcinoma are a lack of clinical classification of the stage of disease at the time of primary therapy, unavailability of ten year follow-up data, and differences in methods of evaluating results of treatment in these young women as compared with older patients whose carcinomas were treated in the same manner. Comparing other reported series of young women with breast carcinoma, Earley, Gallagher, and Chapman [2] claim 68 per cent five year survival in patients with Stage I lesions yet admit that they reclassified all lesions that proved to have axillary metastases into Stage II for purposes of their study. Thus, their Stage I patients are not clinically staged but rather histologically staged lesions, a highly select group, which cannot be compared with a group of patients that is staged prior to the inception of therapy. Yet their quoted five year survival for these patients, 68 per cent of nineteen patients, can hardly be considered favorable, nor is it comparable to the expected outcome for histologically verified Stage A lesions without axillary metastases, for which pa-
The Amwican
Journal ol Surgery
Breast Cancer in Young Women
tients Haagensen [II] has reported a ten year survival of 76.5 per cent in 418 patients. Our present study demonstrates a ten year survival of 66.7 per cent for women with Stage A lesions who prove to have no axillary metastases, and we would agree that the survival of these highly selected patients with most favorable lesions may not be different from that of older women with similarly favorable cancers. However, the unfortunate group of young women with metastases to the regional lymph nodes demonstrates a decreased ten year survival when compared with older women with similar axillary node metastases, unless the older women are shown to have more than four or more involved axillary lymph nodes, in which case their outlook is just as grim as that of the younger women [1 I]. Horsley, Alrich, and Wright [3], in their study, concluded also that there was no difference in survival between young women (less than 35 years old) and older women, based on their ten year follow-up of forty-two patients. These patients were not staged clinically and were divided only into groups demonstrating positive and negative regional lymph node metastases. Their reported ten year survival of 56 per cent for these women with negative nodes is not equivalent to the 76.5 per cent ten year survival after radical mastectomy reported by Haagensen [111. Moore and Lewis [4] reported 38 per cent five year survival in their patients less than thirty years old, but they did not report ten year survival data, categorized either by clinical stage or lymph node status. Yet they concluded that survival in this group of women was comparable with that of other age groups, based on the 81 per cent five year survival of thirteen patients without lymph node metastases who had been treated by radical mastectomy and the 23 per cent five year survival of those patients with nodal metastases. Birks et al [I] reported 63.8 per cent ten year survival of twenty-two women thirty years and younger with negative regional lymph nodes as compared with 33.3 per cent ten year survival of fifteen women with axillary metastases. Although the survival data for their twenty-two women without nodal metastases are not much different from the data reported herein for patients with Stage A lesions without nodal metastases, concluding that the prognosis of breast cancer in young women is equal to that .in older women does not appear statistically justifiable, based on the survival of only five of fifteen patients with lymph node metastases. In the large series of patients reported by Treves and Holleb [5], including women through the age of thirty-five years, when positive axillary lymph nodes
vohw
131. May 1976
were encountered, the five year survival was only 23.7 per cent, and when the axilla was free from metastasis, the five year survival was 61.7 per cent. When their data were subdivided by age, omitting the women between the ages of thirty-one and thirty-five years-that is, including only women thirty years and younger-then only 51 of 124 patients (41 per cent) survived for five years. Unfortunately, these younger women were not subdivided by lymph node status or clinical stage, nor were ten year survival data reported. These data, showing only 41 per cent five year survival, are not unlike our own data, which reveal ten year survival of 33.3 per cent in all cases. Thus, when the results reported by others are analyzed carefully, the data do not appear to support the conclusion that there is no difference in the prognosis of breast cancer when it is encountered in young women. For the few patients with either clinical stage of disease or lymph node status reported, and ten year survival data available, the data do not indicate a similar outlook for the young women as for the older women. Previous reports do indicate that the likelihood of survival in patients with negative regional lymph nodes is similar to that which we have observed, namely, that about two thirds of the patients in this favorable category will survive for at least ten years without evidence of recurrence or metastasis. Our data indicate, however, that for the patients whose cancers have spread to the axillary lymph nodes, the prognosis is poor. Based on our collected data, should there be some nonoperative technic of ascertaining the histologic status of the axillary lymph nodes, we would have no hesitation about recommending that radical mastectomy be abandoned in favor of irradiation in the young women with known axillary metastases. Unfortunately, such a test is not extant, and even in the best of hands, the clinical assessment of the axilla proves accurate in only two thirds of patients [9]. Interestingly enough, but perhaps due to the retrospective design of our own study, the clinical assessment of the axilla in the patients reported here was less accurate than that usually reported, and Stage A and B patients were found to have metastases to the axillary lymph nodes in greater numbers than expected [9]. This did not affect the outcome since our data have been tabulated according to the frequency of axillary node metastases as well as clinical stage of disease. Thus, we still advocate meticulous radical mastectomy as the treatment of choice for young women with Stage A or B breast cancer, recognizing that the prognosis, if any lymph node metastases are verified, is poor. It is important to emphasize that the lesions
573
Schwartz
and Zeok
must be staged clinically, before the initiation of therapy, not after the axillary contents have been examined in the surgical pathology laboratory. It appears that our only present hope for an improved prognosis in these young women with mammary cancer depends on earlier detection. Those young women with an increased risk of having breast cancer should be examined just as frequently and thoroughly as older women. Careful physical examination cannot be begun at too early an age for these women, as they enter the childbearing period, and should be continued at quarterly intervals throughout their lives. Summary
knowledge the assistance of C. D. Haagensen, MD, Professor Emeritus of Clinical Surgery, College of Physicians & Surgeons of Columbia University, New York City, who reviewed this manuscript in the course of its preparation. References 1. Birks DM. Crawford GM, Ellison LG. Johnstone FRC: Carcinoma 2.
3.
4.
The clinical records of 111 young women with breast carcinoma aged thirty years and younger have been analyzed with respect to the clinical stage of disease when first seen, the histologic status of the regional lymph nodes, and ten year survival. Survival in these young women with mammary carcinoma is equivalent to that of older women when the cancer is in its earliest stage, Stage A, but only if the regional lymph nodes are free from metastatic disease. Once the regional lymph nodes are involved by cancer, the prognosis for these young women is indeed dismal, with less than 20 per cent ten year survival regardless of clinical stage.
5.
6. 7.
8. 9.
10.
11.
Acknowledgment:
574
The
authors
gratefully
ac-
of the breast in women 30 years of age or less. SurgGyneco/ Obstet 137: 21, 1973. Earley TK. Gallagher JQ. Chapman KE: Carcinoma of the breast in women under thirty years of age. Am J Surg 118: 832 1969. Horsley JS Ill. Alrich EM, Wright CB: Carcinoma of the breast in women 35 years of age or younger. Ann Surg 169: 839, 1969. Moore SW, Lewis RJ: Carcinoma of the breast in women 30 years of age and under. Surg Gynecol Obstet 119: 1253, 1964. Treves N, Holleb Al: A report of 549 cases of breast cancer in women 35 years of age or younger. Surg Gynecol Obstet 107: 271, 1958. Whlte TT: Prognosis of breast cancer for pregnant and nursing women. Surg Gynecol Of&et 100: 661, 1955. Kleinfeld G, Haagensen CD. Cooley E: Age and menstrual status as prognostic factors in carcinoma of the breast. Ann Surg 157: 600, 1963. Haagensen CD: Diseases of the Breast, 2nd ed. Philadelphia, WB Saunders, 1971, 655. Haagensen CD, Cooley E, Miller E, et al: Treatment of early mammary carcinoma-a cooperative international study. Ann Surg 170: 675, 1969. Mauser JS, Shimkin MD, Moss NH, Rosemont GP: Cancer of the breast in Philadelphia hospitals 195 l- 1964. Cancer 23: 260. 1969. Haagensen CD: The choice of treatment for operable carcinoma of the breast. Surgery76: 685, 1974.
The American Journal of Surgery
MD, Philadelphia,
John V. Zeok, MD,* Philadelphia,
Pennsylvania
Pennsylvania
The optimal primary treatment for mammary carcinoma is a subject of contemporary controversy, with staunch and knowledgeable advocates of widely disparate modes of therapy. For the physician who encounters an unfortunate young woman with breast cancer, this controversy becomes even more frustrating, because of even wider variations in survival reported for these patients, regardless of the therapy chosen. Opinions concerning the relative virulence of breast carcinoma in young women aged thirty years or younger differ markedly. Some regard breast cancer in this age group no different from that disease in older women [I-6], whereas others consider breast cancer in these young women more frequently and/or more rapidly fatal [ 71. Although several contemporary authors have concluded that these young women are not necessarily doomed, Kleinfeld, Haagensen, that relative youth and Cooley [7] h ave commented affects prognosis almost as much as the status of the axillary lymph nodes, and their data imply a poor prognosis in these women. More recently, Haagensen [B] has noted survival in women less than thirty years old only when the disease was noted in its earliest stage, Stage A, and even in these women, ten year survival was only 51 per cent, as compared with more than 70 per cent survival in women of all ages with Stage A cancers treated by radical mastectomy. Part of the controversy regarding optimal treatment for young women with breast cancer must relate to the relatively infrequent occurrence of the disease in this age group, representing less than 2 per cent of all mammary carcinomas. Except for the series of women thirty-five years and younger reported by Treves and Holleb [5], all of the reported series discuss only small numbers of patients, thus making valid statistical observations difficult to achieve. Additionally, there is little mention in the literature of the clinical stage of disease at the time these young
From the Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania. This work was supported in part by a clinica~fellowshipirom the American Cancer Society (JVZ). Reprint requests should be addressed to Gordon F. Schwartz. MD, Department of Surgery, Jefferson Medical College, 1025 Walnut Street, Philadelphia, Pennsylvania 19107. ’ Formerly Chief Resident in Surgery and Clinical Fellow of the American Cancer Society.
570
women received their primary therapy. The necessity for accurate clinical staging of mammary carcinoma to compare different methods of treatment in different groups of patients has been emphasized in the literature [9]. Because the total number of young women with breast cancer has been small, there have been few attempts at further subdivision of this already small number into even smaller subgroups based on clinical stage of disease and/or lymph node status. Material
and Methods
In 1951, the Philadelphia County Medical Society organized a breast cancer registry as part of an attempt to reduce delay in the diagnosis and treatment of mammary carcinoma. During the period of its operation, 1951 through 1964, the registry recorded 9,003 patients [IO]. It has been estimated previously that these records include 85 to 90 per cent of all breast cancers encountered in Philadelphia during this period of time [IO]. This registry was culled and charts were reviewed for all patients thirty years of age and younger who were encountered between the inception of the program in 1951 and December 31, 1963. The age of record was the patient’s age at time of initial definitive therapy; thus, if a patient had had symptoms in her thirtieth year but was treated after her thirty-first birthday, she was not included in the study group. Similarly, primary therapy must have been initiated prior to January 1,1964, to insure a minimal follow-up period of ten years, since five year survival data are considered inconclusive in the evaluation of patients with mammary carcinoma [8]. Review of the Philadelphia County Medical Society breast cancer registry yielded the records of 111 patients thirty years or younger with histologically documented carcinoma of the breast for whom ten year follow-up was complete. Several additional patients encountered during the same time period but lost to follow-up, were not included in the study. Hospital records were reviewed, and the clinical data available were used to classify all patients into one of four clinical stages according to the Columbia Clinical Classification, based on Haagensen’s criteria, which are reiterated in Table I [9]. If the clinical data were insufficient to enable staging according to the Columbia Classification, the lesion was designated as “unspecified clinical classification” and tallied as such. Scrutiny of the pathology reports of each patient allowed further subdivision within each clinical stage into those patients with negative axillary lymph nodes and those patients whose
The American Journal ol Surgery
Breast Cancer in Young Women
TABLE I
Columbia Clinical Classification [91
Stage
No skin edema, ulceration, or solid fixation of tumor to chest wall. Axillaty nodes not clinically involved. Stage B: No skin edema, ulceration, or solid fixation of tumor to chest wall. Clinically involved axillary nodes-but less than 2.5 cm in transverse diameter and not fixed to overlying skin or deeper structures of axilla. Stage C: Any one of the five grave signs of advanced breast carcinoma: 1. Edema of skin of limited extent (involving less than one third of the skin over the breast). 2. Skin ulceration. 3. Solid fixation of tumor to chest wall. 4. Massive involvement of axillary lymph nodes: a. A single node, or group of fused nodes, measuring 2.5 cm or more in transverse diameter. b. A chain of nodes extending high into the axilla. 5. Fixation of the axillary nodes to overlying skin or deeper structures of axilla. Stage 0: All other patients with more advanced breast carcinoma, including: 1. A combination of any two or more of the five grave signs listed above in Stage C. 2. Extensive edema of skin (involving more than one third of the skin over the breast). 3. Satellite skin nodules. 4. The inflammatory type of carcinoma. 5. Clinically involved supraclavicular lymph nodes. 6. Internal mammary metastases as evidenced by a parasternal tumor. 7. Edema of the arm. 8. Distant metastases. A:
lymph nodes contained foci of metastatic carcinoma. Patients not undergoing radical mastectomy or whose pathology records did not note the status of the axillary nodes were recorded as “axillary nodes unspeci-
axillary
fied.” Survival data were thus obtained for patients in all four clinical stages with and without axillary node metastases.
Results Tabulation of the results of this study are summarized in Tables II and III. Of the 111 patients followed for at least ten years, 66 (59.5 per cent) were classified as Stage A, 21 (18.9 per cent) as Stage B, 10 (9.0 per cent) as Stage C, and 7 (6.3 per cent) as Stage D; 7 patients (6.3 per cent) were unable to be classified clinically from the available data and were therefore listed as “unspecified clinical classification.” Thus, a majority of these young women, 87 (78.4 per cent), had what would be considered generally as early or not locally advanced mammary carcinoma, that is, Stage A or B. With regard to treatment, almost all patients in Stages A, B, and C underwent radical mastectomy. One patient with Stage A disease had a modified radical mastectomy, and one patient with Stage C disease had a simple mastectomy, followed by oophorectomy and adrenalectomy as her primary definitive treatment. Most of the Stage D patients did not undergo radical mastectomy because of the known extent of their disease. Postoperative irradiation was administered to many of the patients with Stage A, B, and C carcinomas. Several patients
v-
131, May 1976
in these stages were also subjected to prophylactic surgical castration as part of their initial definitive treatment. The status of axillary lymph nodes in the patients subjected to radical mastectomy is noted in Table II. Of the sixty-six patients with Stage A carcinoma, 40.9 per cent had negative lymph nodes and 39.4 per cent had at least one axillary lymph node containing metastatic carcinoma. The remainder had no mention made of the lymph node status in the pathology report, or the data were unretrievable. Of the patients with Stage B mammary carcinoma, 9.5 per cent had no axillary lymph node involvement, 85 per cent had at least one positive lymph node, and 4.5 per cent were unspecified as to lymph node status. Only one patient with Stage C disease (10 per cent) had no involved lymph nodes, although 40 per cent of this group had unspecified axillary involvement. Of the ten Stage C patients five (50 per cent) had at
TABLE II
Stage A 6 C
Incidence of Axillary Lymph Node Metastasis No Nodes Involved 27 (40.9%) 2 (9.5%) 1 (10.0%)
Nodes
Nodes
Involved
Unspecified
26 (39.4%) 18 (85.7%) 5 (50.0%)
13 (19.7%) 1 (4.8%) 4 (40.0%)
D” Unclassified* * Lymph node status unknown because axillary tion is rarely performed or data are incomplete.
dissec-
571
Schwartz and Zeok
TABLE I II
10 Year Survival Related to Clinical Stage of Disease and Axillary Node Metastasis Total Number of Patients
Number of Survivors
Stage A No Nodes involved Nodes Involved Nodes Unspecified Total Stage A
27
18 (66.7%)
26 13 66
2 (7.7%) 7 (53.8%) 27 (40.9%)
Stage B No Nodes Involved Nodes Involved Nodes Unspecified
2 18 1
0 6 (33.3%) 0
21
6 (28.6%)
1 5 4 10
1 (100%) 0 1 (25.0%) 2 (20.0%)
Total
Stage B
Stage C No Nodes Involved Nodes Involved Nodes Unspecified Total Stage C Total
Stage D*
Unclassified
by Stage*
that
0
7
2 (28.6%)
111
Grand Total * Indicates ascertained.
7
status of axillary
lymph
37 (33.3%) nodes was not
least one positive axillary lymph node. Of the patients with Stage D carcinoma, two underwent radical mastectomy and both had many involved lymph nodes in their axillae. Survival data according to stage of disease are recorded in Tables III. Survival for all patients in Stages A through D were 40.9,28.6,20, and 0 per cent, respectively. When patients were subdivided by lymph node status, nineteen of the thirty patients without lymph node metastases (63.3 per cent) survived, regardless of the clinical stage of disease. However, of the forty-nine patients with involved axillary lymph nodes, only eight (16.3 per cent) survived, regardless of stage of disease, even though a majority of the forty-nine patients were in Stages A and B. The ten year survival for patients with Stage A carcinoma without axillary lymph node metastases was 66.6 per cent, but of the twenty-six patients with Stage A carcinoma with axillary lymph node metastases, only two patients (7.7 per cent) were alive at the end of ten years. Of the entire group of 111 patients, 37 (33.3 per cent) were alive ten years after primary therapy for their breast carcinoma.
Comments
Excepting the large series reported by Treves and Holleb [5] on patients thirty-five years of age and
572
younger, this group of 111 patients, all aged thirty years or younger, represents the largest group of patients in this age group, clinically classified as to stage of disease when initially treated and subsequently followed for at least ten years. The survival data presented herein vary considerably from most other reported studies except for those patients reported by Haagensen [8], who reported fifty-nine patients less than thirty years old encountered at the Columbia-Presbyterian Medical Center between 1912 and 1960. Their overall ten year survival was 30 per cent, with 51 per cent of the patients with Stage A carcinomas surviving ten years after radical mastectomy. Paralleling our own experience, fourteen of twenty-two Haagensen’s Stage A patients (63.6 per cent) without axillary metastases survived ten years after radical mastectomy, whereas only two of nine patients (22.2 per cent) with axillary metastases, despite their Stage A clinical classification, survived ten years. Reviewing the results of treatment of breast carcinoma in these women aged thirty years and younger, we noted several points. With the exception of one patient who underwent modified radical mastectomy, the only patients who survived ten years were treated by radical mastectomy. Secondly, of the eight patients who survived ten years despite the presence of positive axillary lymph nodes, only one patient had a primary lesion larger than 3.0 cm in diameter, and four of these eight surviving patients had lesions 2.0 cm or smaller in diameter. Criticisms common to most reports of younger women with breast carcinoma are a lack of clinical classification of the stage of disease at the time of primary therapy, unavailability of ten year follow-up data, and differences in methods of evaluating results of treatment in these young women as compared with older patients whose carcinomas were treated in the same manner. Comparing other reported series of young women with breast carcinoma, Earley, Gallagher, and Chapman [2] claim 68 per cent five year survival in patients with Stage I lesions yet admit that they reclassified all lesions that proved to have axillary metastases into Stage II for purposes of their study. Thus, their Stage I patients are not clinically staged but rather histologically staged lesions, a highly select group, which cannot be compared with a group of patients that is staged prior to the inception of therapy. Yet their quoted five year survival for these patients, 68 per cent of nineteen patients, can hardly be considered favorable, nor is it comparable to the expected outcome for histologically verified Stage A lesions without axillary metastases, for which pa-
The Amwican
Journal ol Surgery
Breast Cancer in Young Women
tients Haagensen [II] has reported a ten year survival of 76.5 per cent in 418 patients. Our present study demonstrates a ten year survival of 66.7 per cent for women with Stage A lesions who prove to have no axillary metastases, and we would agree that the survival of these highly selected patients with most favorable lesions may not be different from that of older women with similarly favorable cancers. However, the unfortunate group of young women with metastases to the regional lymph nodes demonstrates a decreased ten year survival when compared with older women with similar axillary node metastases, unless the older women are shown to have more than four or more involved axillary lymph nodes, in which case their outlook is just as grim as that of the younger women [1 I]. Horsley, Alrich, and Wright [3], in their study, concluded also that there was no difference in survival between young women (less than 35 years old) and older women, based on their ten year follow-up of forty-two patients. These patients were not staged clinically and were divided only into groups demonstrating positive and negative regional lymph node metastases. Their reported ten year survival of 56 per cent for these women with negative nodes is not equivalent to the 76.5 per cent ten year survival after radical mastectomy reported by Haagensen [111. Moore and Lewis [4] reported 38 per cent five year survival in their patients less than thirty years old, but they did not report ten year survival data, categorized either by clinical stage or lymph node status. Yet they concluded that survival in this group of women was comparable with that of other age groups, based on the 81 per cent five year survival of thirteen patients without lymph node metastases who had been treated by radical mastectomy and the 23 per cent five year survival of those patients with nodal metastases. Birks et al [I] reported 63.8 per cent ten year survival of twenty-two women thirty years and younger with negative regional lymph nodes as compared with 33.3 per cent ten year survival of fifteen women with axillary metastases. Although the survival data for their twenty-two women without nodal metastases are not much different from the data reported herein for patients with Stage A lesions without nodal metastases, concluding that the prognosis of breast cancer in young women is equal to that .in older women does not appear statistically justifiable, based on the survival of only five of fifteen patients with lymph node metastases. In the large series of patients reported by Treves and Holleb [5], including women through the age of thirty-five years, when positive axillary lymph nodes
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were encountered, the five year survival was only 23.7 per cent, and when the axilla was free from metastasis, the five year survival was 61.7 per cent. When their data were subdivided by age, omitting the women between the ages of thirty-one and thirty-five years-that is, including only women thirty years and younger-then only 51 of 124 patients (41 per cent) survived for five years. Unfortunately, these younger women were not subdivided by lymph node status or clinical stage, nor were ten year survival data reported. These data, showing only 41 per cent five year survival, are not unlike our own data, which reveal ten year survival of 33.3 per cent in all cases. Thus, when the results reported by others are analyzed carefully, the data do not appear to support the conclusion that there is no difference in the prognosis of breast cancer when it is encountered in young women. For the few patients with either clinical stage of disease or lymph node status reported, and ten year survival data available, the data do not indicate a similar outlook for the young women as for the older women. Previous reports do indicate that the likelihood of survival in patients with negative regional lymph nodes is similar to that which we have observed, namely, that about two thirds of the patients in this favorable category will survive for at least ten years without evidence of recurrence or metastasis. Our data indicate, however, that for the patients whose cancers have spread to the axillary lymph nodes, the prognosis is poor. Based on our collected data, should there be some nonoperative technic of ascertaining the histologic status of the axillary lymph nodes, we would have no hesitation about recommending that radical mastectomy be abandoned in favor of irradiation in the young women with known axillary metastases. Unfortunately, such a test is not extant, and even in the best of hands, the clinical assessment of the axilla proves accurate in only two thirds of patients [9]. Interestingly enough, but perhaps due to the retrospective design of our own study, the clinical assessment of the axilla in the patients reported here was less accurate than that usually reported, and Stage A and B patients were found to have metastases to the axillary lymph nodes in greater numbers than expected [9]. This did not affect the outcome since our data have been tabulated according to the frequency of axillary node metastases as well as clinical stage of disease. Thus, we still advocate meticulous radical mastectomy as the treatment of choice for young women with Stage A or B breast cancer, recognizing that the prognosis, if any lymph node metastases are verified, is poor. It is important to emphasize that the lesions
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must be staged clinically, before the initiation of therapy, not after the axillary contents have been examined in the surgical pathology laboratory. It appears that our only present hope for an improved prognosis in these young women with mammary cancer depends on earlier detection. Those young women with an increased risk of having breast cancer should be examined just as frequently and thoroughly as older women. Careful physical examination cannot be begun at too early an age for these women, as they enter the childbearing period, and should be continued at quarterly intervals throughout their lives. Summary
knowledge the assistance of C. D. Haagensen, MD, Professor Emeritus of Clinical Surgery, College of Physicians & Surgeons of Columbia University, New York City, who reviewed this manuscript in the course of its preparation. References 1. Birks DM. Crawford GM, Ellison LG. Johnstone FRC: Carcinoma 2.
3.
4.
The clinical records of 111 young women with breast carcinoma aged thirty years and younger have been analyzed with respect to the clinical stage of disease when first seen, the histologic status of the regional lymph nodes, and ten year survival. Survival in these young women with mammary carcinoma is equivalent to that of older women when the cancer is in its earliest stage, Stage A, but only if the regional lymph nodes are free from metastatic disease. Once the regional lymph nodes are involved by cancer, the prognosis for these young women is indeed dismal, with less than 20 per cent ten year survival regardless of clinical stage.
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6. 7.
8. 9.
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Acknowledgment:
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of the breast in women 30 years of age or less. SurgGyneco/ Obstet 137: 21, 1973. Earley TK. Gallagher JQ. Chapman KE: Carcinoma of the breast in women under thirty years of age. Am J Surg 118: 832 1969. Horsley JS Ill. Alrich EM, Wright CB: Carcinoma of the breast in women 35 years of age or younger. Ann Surg 169: 839, 1969. Moore SW, Lewis RJ: Carcinoma of the breast in women 30 years of age and under. Surg Gynecol Obstet 119: 1253, 1964. Treves N, Holleb Al: A report of 549 cases of breast cancer in women 35 years of age or younger. Surg Gynecol Obstet 107: 271, 1958. Whlte TT: Prognosis of breast cancer for pregnant and nursing women. Surg Gynecol Of&et 100: 661, 1955. Kleinfeld G, Haagensen CD. Cooley E: Age and menstrual status as prognostic factors in carcinoma of the breast. Ann Surg 157: 600, 1963. Haagensen CD: Diseases of the Breast, 2nd ed. Philadelphia, WB Saunders, 1971, 655. Haagensen CD, Cooley E, Miller E, et al: Treatment of early mammary carcinoma-a cooperative international study. Ann Surg 170: 675, 1969. Mauser JS, Shimkin MD, Moss NH, Rosemont GP: Cancer of the breast in Philadelphia hospitals 195 l- 1964. Cancer 23: 260. 1969. Haagensen CD: The choice of treatment for operable carcinoma of the breast. Surgery76: 685, 1974.
The American Journal of Surgery
