749
CHANGING PATTERNS OF BREAST CANCER* JEROME A. URBAN, M.D. Attending Surgeon Memorial Hospital for Cancer and Allied Diseases Memorial Sloan-Kettering Cancer Center New York, N.Y.
I NCREASING numbers of patients are being seen with what might be called "minimal" breast cancer (to be defined later) through public awareness and the use of improved diagnostic aids-primarily mammography. At the Memorial Sloan-Kettering Cancer Center the average size of the primary tumor, as measured in the pathology laboratory, of 1,785 primary operable breast cancers treated by us, has diminished from 3.2 cm. in 1955 to 2 cm. in 1974. The incidence of metastases to the axillary nodes has diminished only slightly-from 50% to 42% during this same interval. However, the extent of involvement and the distribution of metastatic disease in the axilla has improved markedly, with a significant drop in apical node involvement. More than 40% of our "minimal" breast cancers have been found through mammography. This improvement in patient population with more efficient detection of early, more localized lesions, represents a tremendous potential for improved control of this disease. PRIMARY SURGERY In planning the surgical treatment of primary breast cancer one must consider its multicentric origin and regional spread to the axillary and internal mammary lymph nodes.1 No single operative procedure is ideal for all breast cancers. The scope of surgery should be correlated with the clinical and pathological extent of disease in the individual patient, with the aim of removing all tumor present in the breast and regional nodes while preserving appearance and function to the utmost. The primary goal of therapy must remain the complete removal of the cancer. Three operative procedures have been utilized: modified radical mastectomy, radical mastectomy, and extended radical mastectomy. With this *Presented as part of a Conference on Advances in Primary Care held by the Committee on Medical Education of the New York Academy of Medicine June 8, 1977.
Vol. 53, No. 8, October 1977
750
J. A. URBAN
750I.
combined approach, a 10-year survival rate of 61% with 7.7% local recurrence has been attained in a consecutive group of 565 patients with proved primary breast cancer treated by us. Forty percent of these patients had axillary node involvement. The best salvage is obtained in patients with "minimal" breast cancers-noninfiltrating, in situ cancers, and infiltrating cancers less than 1 cm. in measured diameter, which show no axillary metastases on clinical examination. Ten years after modified radical mastectomy 97% of these optimal patients are alive and free of disease. When more extensive cancers are present, particularly when axillary lymph node metastases are found, the extended radical mastectomy has proved more effective in achieving long-term control-54% of patients with axillary node metastases surviving 10 years after the extended procedure, 48% of these patients also having internal mammary lymphnode metastases. An increasing number of patients who can be treated adequately by less than a radical mastectomy are being encountered. Close liason with a competent pathologist must be combined with careful clinical judgement to select the proper operative procedure for each patient. Because the patients now being encountered have less extensive cancers, statistics covering therapeutic results, which are based on current populations of patients, cannot be compared with previous data unless all data are based on accurate hard facts concerning the extent of disease-size of tumor, nodal status, etc. EARLY DIAGNOSIS
Mammography when done with excellent technique and interpreted with care has been a tremendous help in detecting localized breast cancers during their early stages of development. Review of primary operable breast-cancer patients at the Sloan Kettering Cancer Institute, who were examined preoperatively by mammography, demonstrate little difference in the rate of detection of breast cancer in patients 50 years of age and under as compared with those more than 50 years of age. There has been much recent hysteria concerning the potential dangers to the patient of repeated x-ray exposure through repeated mammographic screening. Unfortunately, this undue publicity has affected the utilization of mammography in symptomatic patients as well. The current criticism of mammographic screening is based upon the techniques and results encountered more than 10 years ago in a study by the Health Insurance Plan of Greater New York.3 Since Bull. of N.Y. Acad. of Med.
PATTERNS OF BREAST CANCER
751
then the rate of detection of breast cancer by mammography has increased tremendously-particularly in the younger age group-while the degree of radiation exposure which the patient encounters has diminished to approximately 1/10 of that encountered 10 years ago.4 The benefits of mammography, as currently practiced, weighed against the theoretical risk of x-ray exposure, have improved some 30 to 40 fold when compared with techniques utilized 10 years ago, when radiological techniques were primitive, exposure greater, and detection less effective, particularly in young women. Contralateral biopsy5 of the breast has contributed to the early detection of minimal cancers. Approximately 1/3 of such cancers encountered in my own practice were found through contralateral biopsy done at the time of mastectomy for a known breast cancer. A great majority of these lesions were not detected preoperatively by careful physical examination or mammography.
DETECTION
Self-examination of the breast by the patient plus careful physical examination by her physician during routine examination have been helpful in detection of breast cancers. However, this technique is limited in its effectiveness because most breast cancers cannot be detected by this method until they have attained a significant size and have been present for a comparatively long time. Nevertheless, routine, methodical, careful physical examination of the breast by the physician as well as by the patient should be encouraged since it does contribute to the early detection of this disease. We have no single method for detecting breast cancer with the accuracy which approaches the reliability of the Papanicolaou smear in detecting early cancer of the cervix. It is difficult to detect minimal breast cancer, but all efforts in this direction must be encouraged. In order to obtain the maximum detection of breast cancer at its earliest stage of development all available methods must be combined and repeated frequently. Early detection of breast cancer, while it is limited to the breast or shows minimal involvement of regional nodes, combined with adequate primary therapies, are the most important controllable factors in effecting cure. Breast cancers are not systemic during their early stages, and systemic therapy is not necessary to achieve cure in these lesions. Vol. 53, No. 8, October 1977
752
J. A. URBAN
752J.AUR
BIOLOGICAL MARKERS
Estrogen-binding determination and progesterone binding analysis represent the most significant practical biological markers which have been developed in recent years. These data can separate patients with cancer of the breast into two groups. Approximately 55 to 60% of patients whose estrogen-binding factors are positive will be responsive to hormone manipulation through additive or ablative procedures when systemic spread of disease is present. In contrast, only about 5% of patients with negative estrogen binding will respond to these therapies. When both estrogen binding and progesterone binding are positive, 80% of patients will respond to hormonal manipulation. Determination of estrogen binding and, eventually, progesterone binding as well, should become an integral part of the laboratory data obtained on all patients with primary breast cancer at the time of initial treatment. ADJUVANT THERAPY
Adjuvant multichemotherapy is an experimental procedure. It should not replace or minimize the role of primary surgical treatment, but should be utilized as an addition to the optimum primary surgical procedure for each patient. This therapy must be conducted under carefully controlled conditions, and preferably should be an integral part of controlled clinical studies to evaluate its long-term benefits as well as potential complications properly. It should be applied primarily to patients who have poor prognoses because of the extent of disease encountered during primary treatment. The long-term complications of aggressive multichemotherapy are still unknown. There is no doubt that a delay in the appearance of recurrent disease can be effected through its use. Long-term effects with regard to ultimate cure are still to be evaluated. At present, at three years after treatment there is no significant difference in rates of recurrence or survival6 in postmenopausal patients with primary breast cancer and regional axillary node metastases who were treated by radical mastectomy plus CMF (Cytoxan, Methotrexate, 5 FU) as compared with a controlled group who did not receive CMF. In the premenopausal patients in a similar category a definite prolongation of the disease-free interval is still present at three years in those receiving CMF. Following such adjuvant chemotherapy 78% of the premenopausal patients have become amenorrheic. Although a critical attitude should be maintained toward the management by adjuvant multichemotherapy of patients with more advanced disease in Bull. of N.Y. Acad. of Med.
PATTERNS OF BREAST CANCER
753
the breast and regional nodes, an overwhelming need exists for an effective systemic therapy for them-many already have occult systemic spread of tumor at the time of first treatment. Further efforts in this field must be pursued aggressively under carefully controlled conditions. REFERENCES
1.
2.
3.
4.
Urban, J. A. and Castro, E. B.: Selecting variations in extent of surgical procedure for breast cancer. Cancer 28:1615-23, 1971. Wanebo, H. J., Huvos, A. G., and Urban, J. A.: Treatment of minimal breast cancer. Cancer 23:349-57, 1974. Shapiro, S.: Experience of the HIP Study, Washington D.C. NHI Symposium "Report to the Profession". November 1976. Pomerance, W.: Current Experience of
Vol. 53, No. 8, October 1977
the Breast Screening Centers. NHI Symposium Report to the Profession. November 1976, Washington, D.C. 5. Urban, J. A.: Bilaterality of cancer of the breast-Biopsy of the opposite breast. Cancer 20:1867-70, 1967. 6. Bonadonna, G.: Current results of Adjuvant Multichemotherapy in Primary Breast Cancer. Presented at the NHI Symposium Report to the Profession, November 1976, Washington, D.C.
CHANGING PATTERNS OF BREAST CANCER* JEROME A. URBAN, M.D. Attending Surgeon Memorial Hospital for Cancer and Allied Diseases Memorial Sloan-Kettering Cancer Center New York, N.Y.
I NCREASING numbers of patients are being seen with what might be called "minimal" breast cancer (to be defined later) through public awareness and the use of improved diagnostic aids-primarily mammography. At the Memorial Sloan-Kettering Cancer Center the average size of the primary tumor, as measured in the pathology laboratory, of 1,785 primary operable breast cancers treated by us, has diminished from 3.2 cm. in 1955 to 2 cm. in 1974. The incidence of metastases to the axillary nodes has diminished only slightly-from 50% to 42% during this same interval. However, the extent of involvement and the distribution of metastatic disease in the axilla has improved markedly, with a significant drop in apical node involvement. More than 40% of our "minimal" breast cancers have been found through mammography. This improvement in patient population with more efficient detection of early, more localized lesions, represents a tremendous potential for improved control of this disease. PRIMARY SURGERY In planning the surgical treatment of primary breast cancer one must consider its multicentric origin and regional spread to the axillary and internal mammary lymph nodes.1 No single operative procedure is ideal for all breast cancers. The scope of surgery should be correlated with the clinical and pathological extent of disease in the individual patient, with the aim of removing all tumor present in the breast and regional nodes while preserving appearance and function to the utmost. The primary goal of therapy must remain the complete removal of the cancer. Three operative procedures have been utilized: modified radical mastectomy, radical mastectomy, and extended radical mastectomy. With this *Presented as part of a Conference on Advances in Primary Care held by the Committee on Medical Education of the New York Academy of Medicine June 8, 1977.
Vol. 53, No. 8, October 1977
750
J. A. URBAN
750I.
combined approach, a 10-year survival rate of 61% with 7.7% local recurrence has been attained in a consecutive group of 565 patients with proved primary breast cancer treated by us. Forty percent of these patients had axillary node involvement. The best salvage is obtained in patients with "minimal" breast cancers-noninfiltrating, in situ cancers, and infiltrating cancers less than 1 cm. in measured diameter, which show no axillary metastases on clinical examination. Ten years after modified radical mastectomy 97% of these optimal patients are alive and free of disease. When more extensive cancers are present, particularly when axillary lymph node metastases are found, the extended radical mastectomy has proved more effective in achieving long-term control-54% of patients with axillary node metastases surviving 10 years after the extended procedure, 48% of these patients also having internal mammary lymphnode metastases. An increasing number of patients who can be treated adequately by less than a radical mastectomy are being encountered. Close liason with a competent pathologist must be combined with careful clinical judgement to select the proper operative procedure for each patient. Because the patients now being encountered have less extensive cancers, statistics covering therapeutic results, which are based on current populations of patients, cannot be compared with previous data unless all data are based on accurate hard facts concerning the extent of disease-size of tumor, nodal status, etc. EARLY DIAGNOSIS
Mammography when done with excellent technique and interpreted with care has been a tremendous help in detecting localized breast cancers during their early stages of development. Review of primary operable breast-cancer patients at the Sloan Kettering Cancer Institute, who were examined preoperatively by mammography, demonstrate little difference in the rate of detection of breast cancer in patients 50 years of age and under as compared with those more than 50 years of age. There has been much recent hysteria concerning the potential dangers to the patient of repeated x-ray exposure through repeated mammographic screening. Unfortunately, this undue publicity has affected the utilization of mammography in symptomatic patients as well. The current criticism of mammographic screening is based upon the techniques and results encountered more than 10 years ago in a study by the Health Insurance Plan of Greater New York.3 Since Bull. of N.Y. Acad. of Med.
PATTERNS OF BREAST CANCER
751
then the rate of detection of breast cancer by mammography has increased tremendously-particularly in the younger age group-while the degree of radiation exposure which the patient encounters has diminished to approximately 1/10 of that encountered 10 years ago.4 The benefits of mammography, as currently practiced, weighed against the theoretical risk of x-ray exposure, have improved some 30 to 40 fold when compared with techniques utilized 10 years ago, when radiological techniques were primitive, exposure greater, and detection less effective, particularly in young women. Contralateral biopsy5 of the breast has contributed to the early detection of minimal cancers. Approximately 1/3 of such cancers encountered in my own practice were found through contralateral biopsy done at the time of mastectomy for a known breast cancer. A great majority of these lesions were not detected preoperatively by careful physical examination or mammography.
DETECTION
Self-examination of the breast by the patient plus careful physical examination by her physician during routine examination have been helpful in detection of breast cancers. However, this technique is limited in its effectiveness because most breast cancers cannot be detected by this method until they have attained a significant size and have been present for a comparatively long time. Nevertheless, routine, methodical, careful physical examination of the breast by the physician as well as by the patient should be encouraged since it does contribute to the early detection of this disease. We have no single method for detecting breast cancer with the accuracy which approaches the reliability of the Papanicolaou smear in detecting early cancer of the cervix. It is difficult to detect minimal breast cancer, but all efforts in this direction must be encouraged. In order to obtain the maximum detection of breast cancer at its earliest stage of development all available methods must be combined and repeated frequently. Early detection of breast cancer, while it is limited to the breast or shows minimal involvement of regional nodes, combined with adequate primary therapies, are the most important controllable factors in effecting cure. Breast cancers are not systemic during their early stages, and systemic therapy is not necessary to achieve cure in these lesions. Vol. 53, No. 8, October 1977
752
J. A. URBAN
752J.AUR
BIOLOGICAL MARKERS
Estrogen-binding determination and progesterone binding analysis represent the most significant practical biological markers which have been developed in recent years. These data can separate patients with cancer of the breast into two groups. Approximately 55 to 60% of patients whose estrogen-binding factors are positive will be responsive to hormone manipulation through additive or ablative procedures when systemic spread of disease is present. In contrast, only about 5% of patients with negative estrogen binding will respond to these therapies. When both estrogen binding and progesterone binding are positive, 80% of patients will respond to hormonal manipulation. Determination of estrogen binding and, eventually, progesterone binding as well, should become an integral part of the laboratory data obtained on all patients with primary breast cancer at the time of initial treatment. ADJUVANT THERAPY
Adjuvant multichemotherapy is an experimental procedure. It should not replace or minimize the role of primary surgical treatment, but should be utilized as an addition to the optimum primary surgical procedure for each patient. This therapy must be conducted under carefully controlled conditions, and preferably should be an integral part of controlled clinical studies to evaluate its long-term benefits as well as potential complications properly. It should be applied primarily to patients who have poor prognoses because of the extent of disease encountered during primary treatment. The long-term complications of aggressive multichemotherapy are still unknown. There is no doubt that a delay in the appearance of recurrent disease can be effected through its use. Long-term effects with regard to ultimate cure are still to be evaluated. At present, at three years after treatment there is no significant difference in rates of recurrence or survival6 in postmenopausal patients with primary breast cancer and regional axillary node metastases who were treated by radical mastectomy plus CMF (Cytoxan, Methotrexate, 5 FU) as compared with a controlled group who did not receive CMF. In the premenopausal patients in a similar category a definite prolongation of the disease-free interval is still present at three years in those receiving CMF. Following such adjuvant chemotherapy 78% of the premenopausal patients have become amenorrheic. Although a critical attitude should be maintained toward the management by adjuvant multichemotherapy of patients with more advanced disease in Bull. of N.Y. Acad. of Med.
PATTERNS OF BREAST CANCER
753
the breast and regional nodes, an overwhelming need exists for an effective systemic therapy for them-many already have occult systemic spread of tumor at the time of first treatment. Further efforts in this field must be pursued aggressively under carefully controlled conditions. REFERENCES
1.
2.
3.
4.
Urban, J. A. and Castro, E. B.: Selecting variations in extent of surgical procedure for breast cancer. Cancer 28:1615-23, 1971. Wanebo, H. J., Huvos, A. G., and Urban, J. A.: Treatment of minimal breast cancer. Cancer 23:349-57, 1974. Shapiro, S.: Experience of the HIP Study, Washington D.C. NHI Symposium "Report to the Profession". November 1976. Pomerance, W.: Current Experience of
Vol. 53, No. 8, October 1977
the Breast Screening Centers. NHI Symposium Report to the Profession. November 1976, Washington, D.C. 5. Urban, J. A.: Bilaterality of cancer of the breast-Biopsy of the opposite breast. Cancer 20:1867-70, 1967. 6. Bonadonna, G.: Current results of Adjuvant Multichemotherapy in Primary Breast Cancer. Presented at the NHI Symposium Report to the Profession, November 1976, Washington, D.C.
