Seminars in Surgical Oncology 731 1-313 (1991)
Management of Occult Breast Cancer Presenting as an Axillary Metastasis WILLIAM H. KNAPPER, MD From the Gastric and Mixed Tumor Service and Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New Yo&
The presentation of cancer in an axillary lymph node without an obvious primary site is a diagnostic challenge. This is particularly true in female patients. A diagnosis of metastatic adenocarcinoma consistent with occult breast primary requires further prompt therapy. KEY WORDS:hormonal analysis, mastectomy, bilateral breast cancer, long-term survival
INTRODUCTION The presentation of cancer in an axillary lymph node without an obvious primary site is a challenge to all clinicians. This is particularly true in female patients. Axillary lymphadenopathy is frequently encountered in a number of benign and malignant diseases. Infectious or other benign causes are most common [I]. Lymphoma is the most frequent malignant etiology. Carcinomas of the thyroid, lung, stomach, pancreas, and colorectum may metastasize to axillary lymph nodes. However, these rarely do so as the first presentation of the disease. The discovery of axillary metastases from a clinically occult breast primary is also unusual, but must be constantly considered in female patients.
This situation was first reported by Halsted [2] in 1907, who described three patients, all of whom later developed ipsilateral breast cancer and were treated by mastectomy. Since then, mastectomy has been the standard treatment. Microscopic examination of the removed specimen reveals no malignancy in approximately one-third of these patients.
MEMORIAL SLOAN-KETTERING CANCER CENTER STUDY A recent study [3] by the Breast Service at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City was performed to determine if recent advances in mammographic techniques and steroid receptor analysis of specimens have aided in the diagnosis of occult stage I1 breast cancer. The role of breast DIAGNOSIS preservation and possible survival benefit of irradiaA woman with an enlarged axillary node should re- tion and/or systemic chemotherapy was also evaluceive a thorough history and physical examination ated. Thirty-five (0.35%) of a total of 10,014 patients with particular attention to the skin, the head and treated for primary operable breast cancer at MSKCC neck area, breasts, abdomen, pelvis, and other nodal from 1975 to 1988 presented with axillary metastases basins. Once infectious and other benign causes have only. Twenty-seven patients were postmenopausal, been ruled out and no obvious primary site deterthree were perimenopausal (within 1 year of last pemined, chest roentgenograms and a bilateral two-view riod), and five were postmenopausal. Thirty-two pamammography should be performed. Negative intertients had preoperative mammograms still available pretation of these films indicates prompt excision of for interpretation. Nine were thought to be suspicious the axillary mass. Estrogen and progesterone analysis for an occult breast cancer, of which six were pathoof the specimen, along with histological evaluation, logically positive (Table I) [3]. Perioperative bone are needed. A diagnosis of metastatic adenocarcinoma consistent with occult breast primary requires further Address reprint requests to William Knapper, M.D., Breast Serprompt therapy. Delaying treatment for an observa- vice, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. tion period is potentially dangerous. Q
1991 Wiley-Liss, Inc.
312
Knapper
TABLE I. Mammogram Interpretations Compared With Breast Cancer* Cancer identified in breast (%I) ----_____Totdl
Mammogram _ _-_________ susplclous Normdl
9 23
Positive
____
6 15 Sensitivity Specificity Accuracy
(67) (65) 29%) 73% 44%
Negatibe
3 8
(33) (35)
*Reproduced with permission of the American Medical Associdtion from Baron PL, Moore MP. Kinne DW et al, Occult bredst cancer presenting with axilldry metastases Arch Surg 125 210-214. 1990
scans were obtained in 27 patients, all of which were negative for metastatic disease. No chest roentgenograms were suspicious for malignancy. All other diagnostic tests performed failed to reveal another primary cancer or other metastases. Mastectomy was performed on 28 patients. One of these had bilateral radical mastectomies because of obvious right breast cancer and a suspicious left axillary node. Primary left breast cancer was found in the specimen. Limited resection with axillary dissection and radiation therapy was performed on four patients with a mammographicaliy suspicious quadrant. Two patients had axillary dissection plus irradiation and one underwent quadrantectomy alone, refusing other therapy . Carcinoma was found in 22 (67%) of the breast specimens. Eighteen were invasive and four in situ.
Occult cancer was found in 20 (71%) of the mastectomy specimens and two (40'1/0)of the five segmental resections. Three of the four patients with in situ disease had involvement of all four quadrants of the breast. Of the 22 cancers, ten (45%) were multifocal. Of the nine suspicious mammograms, six (67%) were positive for cancer. Fifteen of 23 patients whose mammograms were interpreted as normal were later found to have occult cancer. Fifty percent of lymph node or breast specimen tests for estrogen receptor were positive. Of those specimens submitted for progesterone receptor (not performed at our institution prior to 1980), 32% were positive. Twenty-two (630/0)were alive and free of disease at the time of this study (November, 1989). Eight (23%) died of their disease and four (1 1%) were alive with disease. One patient died of other causes. Five and 10 year actuarial survival was 75% and 55% overall (Fig. 1). Patients with negative estrogen receptor had a decreased 5 and 10 year survival when compared to patients with positive estrogen receptor. There was no significant difference in 5 year survival for the breast preservation group, or for whether the cancer was found in the breast specimen. Five year survival was similar whether or not postoperative adjuvant chemotherapy and/or hormonal therapy was given. However, there was a higher incidence of post-biopsy axillary disease in the adjuvant patients' group, which indicates possible benefit from adjuvant therapy.
N.35
PROPORTION S U R V I V I N G
I
0.8 0.7
0.6
1 I
0.5
I
I
0.4 0.3
0.2 t
0.1t 01 0
I
I
12
24
36
48
60
72
1
I
1
84
96
108
TIME (mo) Fig. 1. Overall survival of patients with occult breast cancer presenting with axillary metastasis.
120
Occult Breast Cancer in Axillary Node 313
-8-T2N1 Historic
0.4
0
I
I
I
I
I
I
I
I
1
12
24
36
48
60
72
84
96
108
120
TIME (mo) Fig. 2. Survival versus historic controls in patients with occult breast cancer.
SUMMARY When histologic examination of an axillary node reveals adenocarcinoma compatible with a breast primary, and no other primary is obvious, mastectomy Of the remainand'or limited resection Plus ing axillary nodes are indicated. An axillary node which is highly positive for estrogen receptor strongly suggests a breast primary, but negativity of estrogen receptors does not rule Out a breast cancer. Five and 10 year survival rates for patients with occult breast
cancer do not differ significantly from those with a known breast primary and N1 disease (Fig- 2)REFERENCES 1. pierce EH, Gray H, Dockerty MB; Surgical ..jgnificance of,solated axillary adenopathy. Ann Surg 145:10&107, 1957. 2. Halsted W: The results of radical operations for the cure of carcinoma Of the breast. Ann Surg I9O7. 3. Baron PL, Moore MP, Kinne DW, et al.: Occult breast cancer presenting with axillary metastases. Arch Surg 125:210-214, 1990. 46:1-193
Management of Occult Breast Cancer Presenting as an Axillary Metastasis WILLIAM H. KNAPPER, MD From the Gastric and Mixed Tumor Service and Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New Yo&
The presentation of cancer in an axillary lymph node without an obvious primary site is a diagnostic challenge. This is particularly true in female patients. A diagnosis of metastatic adenocarcinoma consistent with occult breast primary requires further prompt therapy. KEY WORDS:hormonal analysis, mastectomy, bilateral breast cancer, long-term survival
INTRODUCTION The presentation of cancer in an axillary lymph node without an obvious primary site is a challenge to all clinicians. This is particularly true in female patients. Axillary lymphadenopathy is frequently encountered in a number of benign and malignant diseases. Infectious or other benign causes are most common [I]. Lymphoma is the most frequent malignant etiology. Carcinomas of the thyroid, lung, stomach, pancreas, and colorectum may metastasize to axillary lymph nodes. However, these rarely do so as the first presentation of the disease. The discovery of axillary metastases from a clinically occult breast primary is also unusual, but must be constantly considered in female patients.
This situation was first reported by Halsted [2] in 1907, who described three patients, all of whom later developed ipsilateral breast cancer and were treated by mastectomy. Since then, mastectomy has been the standard treatment. Microscopic examination of the removed specimen reveals no malignancy in approximately one-third of these patients.
MEMORIAL SLOAN-KETTERING CANCER CENTER STUDY A recent study [3] by the Breast Service at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City was performed to determine if recent advances in mammographic techniques and steroid receptor analysis of specimens have aided in the diagnosis of occult stage I1 breast cancer. The role of breast DIAGNOSIS preservation and possible survival benefit of irradiaA woman with an enlarged axillary node should re- tion and/or systemic chemotherapy was also evaluceive a thorough history and physical examination ated. Thirty-five (0.35%) of a total of 10,014 patients with particular attention to the skin, the head and treated for primary operable breast cancer at MSKCC neck area, breasts, abdomen, pelvis, and other nodal from 1975 to 1988 presented with axillary metastases basins. Once infectious and other benign causes have only. Twenty-seven patients were postmenopausal, been ruled out and no obvious primary site deterthree were perimenopausal (within 1 year of last pemined, chest roentgenograms and a bilateral two-view riod), and five were postmenopausal. Thirty-two pamammography should be performed. Negative intertients had preoperative mammograms still available pretation of these films indicates prompt excision of for interpretation. Nine were thought to be suspicious the axillary mass. Estrogen and progesterone analysis for an occult breast cancer, of which six were pathoof the specimen, along with histological evaluation, logically positive (Table I) [3]. Perioperative bone are needed. A diagnosis of metastatic adenocarcinoma consistent with occult breast primary requires further Address reprint requests to William Knapper, M.D., Breast Serprompt therapy. Delaying treatment for an observa- vice, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. tion period is potentially dangerous. Q
1991 Wiley-Liss, Inc.
312
Knapper
TABLE I. Mammogram Interpretations Compared With Breast Cancer* Cancer identified in breast (%I) ----_____Totdl
Mammogram _ _-_________ susplclous Normdl
9 23
Positive
____
6 15 Sensitivity Specificity Accuracy
(67) (65) 29%) 73% 44%
Negatibe
3 8
(33) (35)
*Reproduced with permission of the American Medical Associdtion from Baron PL, Moore MP. Kinne DW et al, Occult bredst cancer presenting with axilldry metastases Arch Surg 125 210-214. 1990
scans were obtained in 27 patients, all of which were negative for metastatic disease. No chest roentgenograms were suspicious for malignancy. All other diagnostic tests performed failed to reveal another primary cancer or other metastases. Mastectomy was performed on 28 patients. One of these had bilateral radical mastectomies because of obvious right breast cancer and a suspicious left axillary node. Primary left breast cancer was found in the specimen. Limited resection with axillary dissection and radiation therapy was performed on four patients with a mammographicaliy suspicious quadrant. Two patients had axillary dissection plus irradiation and one underwent quadrantectomy alone, refusing other therapy . Carcinoma was found in 22 (67%) of the breast specimens. Eighteen were invasive and four in situ.
Occult cancer was found in 20 (71%) of the mastectomy specimens and two (40'1/0)of the five segmental resections. Three of the four patients with in situ disease had involvement of all four quadrants of the breast. Of the 22 cancers, ten (45%) were multifocal. Of the nine suspicious mammograms, six (67%) were positive for cancer. Fifteen of 23 patients whose mammograms were interpreted as normal were later found to have occult cancer. Fifty percent of lymph node or breast specimen tests for estrogen receptor were positive. Of those specimens submitted for progesterone receptor (not performed at our institution prior to 1980), 32% were positive. Twenty-two (630/0)were alive and free of disease at the time of this study (November, 1989). Eight (23%) died of their disease and four (1 1%) were alive with disease. One patient died of other causes. Five and 10 year actuarial survival was 75% and 55% overall (Fig. 1). Patients with negative estrogen receptor had a decreased 5 and 10 year survival when compared to patients with positive estrogen receptor. There was no significant difference in 5 year survival for the breast preservation group, or for whether the cancer was found in the breast specimen. Five year survival was similar whether or not postoperative adjuvant chemotherapy and/or hormonal therapy was given. However, there was a higher incidence of post-biopsy axillary disease in the adjuvant patients' group, which indicates possible benefit from adjuvant therapy.
N.35
PROPORTION S U R V I V I N G
I
0.8 0.7
0.6
1 I
0.5
I
I
0.4 0.3
0.2 t
0.1t 01 0
I
I
12
24
36
48
60
72
1
I
1
84
96
108
TIME (mo) Fig. 1. Overall survival of patients with occult breast cancer presenting with axillary metastasis.
120
Occult Breast Cancer in Axillary Node 313
-8-T2N1 Historic
0.4
0
I
I
I
I
I
I
I
I
1
12
24
36
48
60
72
84
96
108
120
TIME (mo) Fig. 2. Survival versus historic controls in patients with occult breast cancer.
SUMMARY When histologic examination of an axillary node reveals adenocarcinoma compatible with a breast primary, and no other primary is obvious, mastectomy Of the remainand'or limited resection Plus ing axillary nodes are indicated. An axillary node which is highly positive for estrogen receptor strongly suggests a breast primary, but negativity of estrogen receptors does not rule Out a breast cancer. Five and 10 year survival rates for patients with occult breast
cancer do not differ significantly from those with a known breast primary and N1 disease (Fig- 2)REFERENCES 1. pierce EH, Gray H, Dockerty MB; Surgical ..jgnificance of,solated axillary adenopathy. Ann Surg 145:10&107, 1957. 2. Halsted W: The results of radical operations for the cure of carcinoma Of the breast. Ann Surg I9O7. 3. Baron PL, Moore MP, Kinne DW, et al.: Occult breast cancer presenting with axillary metastases. Arch Surg 125:210-214, 1990. 46:1-193
