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Breast cancer in adolescent females
B r e a s t C a n c e r in A d o l e s c e n t F e m a l e s By Cynthia A. Corpron, C. Thomas Black, S. Eva Singletary, and Richard J. Andrassy Houston, Texas • Reports of breast cancer in adolescent females consist mostly of isolated patients. Because of this, neither the prognosis nor optimal management of the disease in this age group is clear. The authors retrospectively reviewed their 40-year single-institution experience of all patients under 20 years of age who were referred for treatment of newly diagnosed breast cancer. The charts of 16 patients, all females (age range, 13 to 19 years), were reviewed. Four patients found to have cytosarcoma phyllodes and two with tumors metastatic to the breast were excluded from further study. Ten patients had various forms of adenocarcinoma of the breast, including invasive intraductal, invasive Iobular, signet ring, and secretory adenocarcinoma. Four had a family history of breast cancer. The average time from onset of symptoms to diagnosis was 3.7 months. Mammography failed to diagnose cancer in any of the four patients tested, including one with an 8-cm mass. Two patients had stage I tumors, four had stage IIA, two had stage IliA, and two had stage IV. The patients were treated with combinations of surgery, radiation therapy, and chemotherapy. One stage I patient (with bilateral breast cancer) died of radiationinduced sarcoma after treatment; the other stage I patient is alive without disease 15 years after treatment. The 5-year survival rate for stage IIA patients was 50%; that for patients with stage IliA or IV was 0%. Five of the 10 patients presented during the past 10 years. This study constitutes the largest single institution experience with adolescent breast cancer. Adenocarcinoma of the breast, although rare, does occur in adolescent females and must be considered in the differential diagnosis of breast masses in this age group. Appropriate evaluation may necessitate biopsy because mamm o g r a p h y can be unreliable. The outcome for our patients suggests that the prognosis of advanced.stage breast cancer in adolescents may be at least as ominous as that in adult patients. Since several advanced-stage patients presented with large (<5 cm) tumors or had a long delay (up to 13 months) between onset of symptoms and diagnosis, thorough evaluation of a breast mass in an adolescent female should not be postponed.
agement of breast masses in the young patient has been advocated, malignancy must be included in the differential diagnosis. This article reviews a single cancer center's experience with adolescent breast cancer. MATERIALS AND METHODS A review of the data base maintained by the Department of Patient Studies at M.D. Anderson Cancer Center showed that 16 patients under age 20 were referred between 1951 and 1990 with the diagnosis of primary breast cancer. The charts of these patients were reviewed retrospectively. Presentation, tumor histology, stage at time of diagnosis, treatment, and outcome were recorded for all patients.
RESULTS
From the Section of Pediatric Surgery, Department of Surgical Oncology, M.D. Anderson Cancer Center and University of Texas Medical School at Houston, Houston, TX. Presented at the 25th Annual Meeting of the American Pediatric Surgical Association, Tucson, Arizona, May 14-17, 1994. Address reprint requests to Richard J. Andrassy, MD, Division of Pediatric Surgery, 6431 Fannin, Suite 6.264, Houston, TX 77030. Copyright © 1995 by W.B. Saunders Company 0022-3468/95/3002-0030503.00/0
Four of the patients were found to have benign cystosarcoma phyllodes, one had osteosarcoma, and one had metastatic histiocytic lymphoma. These patients were excluded from further review. One patient presented with adenocarcinoma, with features of signet ring histology. This patient had biopsies of several colonic polyps but had no evidence of invasive colon cancer. Pathological review could not exclude possible metastatic disease from an unknown primary colon cancer, although this would be a very unusual site of colon cancer metastasis. Nine patients had infiltrating ductal carcinoma, only one of whom had features suggestive of secretory (juvenile) breast cancer. One patient had infiltrating lobular carcinoma in addition to infiltrating ductal carcinoma. Of the five patients who had documentation of receptor status, estrogen receptors were positive in three patients and negative in two. Progesterone receptors were negative in all five patients. The age at time of presentation ranged from 13 to 19 years (mean, 16.2 years). Five patients were white, four were black, and one was Hispanic. No patient had a history of radiation exposure or previous malignancy. Patients with a family history of breast cancer included one with a positive maternal (premenopausal) history, two with maternal aunts with breast cancer, and one with a maternal great aunt with breast cancer. The time from onset of symptoms until diagnostic biopsy ranged from 1 to 13 months (mean, 3.7 months). The patients were staged according to the AJCC 2 staging system. Two had stage I tumors, four had stage IIA, two had
322
Journa/of Pediatric Surgery, Vo130, No 2 (February), 1995: pp 322-324
Copyright © 1995 by W.B. Saunders Company INDEX WORDS: Breast neoplasms, carcinoma, adolescence.
C
ARCINOMA of the breast is rare in children and adolescents. 1 Although conservative man-
B R E A S T C A N C E R IN A D O L E S C E N T
FEMALES
stage IliA, and two had stage IV. Treatment involved combinations of surgery, radiation therapy, and chemotherapy. One stage I patient (with bilateral breast cancer) died of a radiation-induced sarcoma after treatment; the other stage I patient is alive without disease 15 years later. The stage IIA patients had a five-year survival rate of 50%; all stage IIIA and stage IV patients died within 5 years of diagnosis. Five of the 10 patients presented within the last 10 years. Mammography failed to diagnose cancer in any of the four patients tested, including one with an 8-cm mass. DISCUSSION
Management of a breast mass in a child or adolescent can be difficult. The majority of such breast masses represent benign processes such as abscess, hematoma, cyst or fibroadenoma. 3-6 Several large studies examining breast biopsy findings in patients under 30 years of age showed few or no biopsies positive for breast cancer. 4-6 In two of the largest series, 5.6 no biopsy specimens from patients under 20 years of age were positive for carcinoma of the breast. This has led to a policy of conservative management of breast masses in young patients by many physicians. However, malignancies involving the breast can occur in children and adolescents. 1 Masses in the breasts of pediatric patients can represent metastases from primary lesions such as Hodgkin's and non-Hodgkin's lymphoma, neuroblastoma, and rhabdomyosarcoma. Results of several studies 3,7 suggest that metastatic lesions might be more common than primary lesions in the breast of pediatric patients. Because a breast mass may be the presenting symptom in such patients, biopsy of the mass may lead to early diagnosis of the primary lesion, before the occurrence of other symptoms. In addition, primary breast lesions such as rhabdomyosarcoma and malignant cystosarcoma phyllodes can occur in pediatric patients. 3,7 Although primary carcinoma of the breast is rare in children and adolescents, 74 such cases were found in the world literature. I The present study involves the largest single-institution series of primary breast cancer in adolescents. No risk factors clearly identifying the young patients at risk for malignant breast masses have been determined. Family history of breast cancer, 8 especially hereditary or familial breast cancer, might be a risk factor for early-onset breast cancer. Some investigators have suggested that breast cancer in the young (under age 35) patient may have a better, 1worsC 4~ or similar ~2 prognosis to that in older patients. In addition, patients who present with breast cancer at a
323
ADOLESCENT WITH BREAST MASS
I FOLLOW FOR NO MORE THAN ONE MONTH
I ATTEMPTED ASPIRATION
CLEAR, YELLOW, OR GREEN FLUID AND MASS DISAPPEARS
r
BLOODY OR NO FLUID, MASS NOT RESOLVED
I CONSIDER ULTRASOUND
REPEAT EXAM IN ONE MONTH TEACH BREAST SELF EXAM
l
FINE NEEDLE ASPIRATION BIOPSY
r
OPEN BIOPSY
I IF BIOPSY NEGATIVE, TEACH SELF EXAM
Fig 1.
Evaluation of the adolescent with a breast mass,
young age have an increased risk for the development of second malignancies, tl Because of the small number of patients who present during adolescence, the prognosis is not clear. Although in this study, mammography was not helpful in the diagnosis of breast cancer, recent larger studies 1345 have shown that although mammography might be less sensitive in detecting malignancies in younger patients than in older ones, it may be of some value. In addition, studies have shown that fineneedle aspiration of breast masses in young patients may be helpful in establishing the diagnosis. 15-17 Delays in diagnosis often occur in the adolescent with breast cancer because of hesitancy to perform operative biopsy. Although fine-needle aspiration biopsy is less sensitive than operative biopsy, it might be adequate for most patients. Because adenocarcinoma of the breast, although rare, does occur in adolescent patients, it must be considered in the differential diagnosis of breast masses in this age group. Although mammography may be helpful in some cases, appropriate evaluation may require biopsy. Fine-needle aspiration may be helpful in this setting. Because inappropriate evaluation can lead to a delay in diagnosis, thorough evaluation of breast masses in adolescents is essential. Our recommendations for evaluation are shown in Fig 1. In addition, because several patients in this and other series presented at late stages or with large tumors, adolescent females should be taught and encouraged to practice breast self-examination, and breast examination by a physician should be part of the routine physical examination. This is especially important for patients with a family history of breast cancer. ACKNOWLEDGMENT
The authors thank Catherine Cooksley and Vincent Guinee, MD, for identifyingthe patient population through a search of the data base maintainedby the Department of Patient Studies.
324
CORPRON ET AL
REFERENCES 1. Ashikari H, Jun MY, Farrow JH, et al: Breast carcinoma in children and adolescents. Clin Bull 7:55-62, 1977 2. Beahrs OH, Henson DE, Hattes RV, et al: American Joint Committee on Cancer. Manual for Staging of Cancer (ed 3). Philadelphia, PA, Lippincott, 1988, pp 145-150 3. Greydanus DE, Parks DS, Farrell EG: Breast disorders in children and adolescents. Pediatr Clin North Am 36:601-638, 1989 4. Palmer ML, Tsangaris TN: Breast biopsy in women 30 years old or less. Am J Surg 165:708-712, 1993 5. Ferguson CM, Powell RW: Breast masses in young women. Arch Surg 124:1338-1341, 1989 6. Seltzer MH, Skiles MS: Diseases of the breast in young women. Surg Gynecol Obstet 150:360-362, 1980 7. Rogers DA, Lobe TE, Rao BN, et al: Breast malignancy in children. J Pediatr Surg 29:48-51, 1994 8. Lynch HT, Watson P, Conway T, et al: Breast cancer family history as a risk factor for early onset breast cancer. Breast Cancer Res Treat 11:263-267, 1988 9. de las Rochefordiere A, Asselain B, Campana F, et al: Age as prognostic factor in premenopausal breast carcinoma. Lancet 341:1039-1043, 1993 10. Noyes RD, Spanos WJ, Montague ED: Breast cancer in women aged 30 and under. Cancer 49:1302-1307, 1982
11. Lee CG, McCormick B, Mazumdar M, et al: Infiltrating breast carcinoma in patients age 30 years and younger: Long-term outcome for life, relapse, and second primaly tumors. Int J Rad Oncol Biol Physiot 23:969-975, 1992 12. Muscolino G, Villani C, Bedini AV, et al: Young age is not an ominous prognostic factor in breast cancer patients. Tumori 73:233-235, 1987 13. deParedes ES, Marstellar LP, Eden BV: Breast cancers in women 35 years of age and younger: Mammographic findings. Radiology 177:117-119, 1990 14. Jeffries DO, Adler DD: Mammographic detection of breast cancer in women under the age of 35. Invest Radiol 25:67-71, 1990 15. Ashely S, Royle GT, Corder A, et al: Clinical, radiological and cytological diagnosis of breast cancer in young women. Br J Surg 76:835-837, 1989 16. Yelland A, Grahan MD, Tron PA, et al: Diagnosing breast carcinoma in young women. Br Med J 302:618-620, 1991 17. Gupta RK, Naran S, Buchanan A, et al: Fine-needle aspiration cytology of breast: Its impact on surgical practice with an emphasis on the diagnosis of breast abnormalities in young women. Diagn Cytopathol 4:206-209, 1988
Discus sion K West (Indianapolis, IN): The authors have delineated their almost-40-year experience with a rare problem, but serious problem. Sixty percent of their patients presented with stage I or II disease; however, there was a 70% mortality rate for this group. Additionally, they reinforced the fact that mammography in the adolescent patient is not helpful in differentiating between benign and malignant lesions. What lessons can we learn from this series? Since this covers 40 years, how has your adjunctive therapy changed during this time? You suggested that breast masses in the adolescent should be followed for only 1 month before a biopsy is performed. In other large studies it has been suggested that masses that are not changing should be followed for longer periods. Are there any characteristics that could be identified by ultrasound that could assist in determining the time of biopsy? Can you give us a summary of the progression of these lesions? Did they double in size over a brief period? For the five patients who presented in the last 10 years, has the prognosis improved? (One of your patients with a stage I lesion actually suc-
cunlbed to treatment complications, not the primary disease.) C.A. Cotpron (response): The options of modified mastectomy or segmental mastectomy must be discussed with every patient. Because it has been suggested that some of these patients might have an increased risk for the development of second breast cancers or second malignancies, minimizing radiation exposure may be preferable, and mastecomy with immediate reconstruction may be suggested. Again, this is an individualized decision for the patient and surgeon. Further recommendations for the clinician include suggesting that a very careful family history be taken in all of these patients. With respect to diagnostic modalities, although no large studies have been done in these young patients, our study and others suggest that mammography is not very helpful. Ultrasound examination of the breast may be more helpful, and it is helpful in localizing more suspicious areas for ultrasound-guided biopsy.
agement of breast masses in the young patient has been advocated, malignancy must be included in the differential diagnosis. This article reviews a single cancer center's experience with adolescent breast cancer. MATERIALS AND METHODS A review of the data base maintained by the Department of Patient Studies at M.D. Anderson Cancer Center showed that 16 patients under age 20 were referred between 1951 and 1990 with the diagnosis of primary breast cancer. The charts of these patients were reviewed retrospectively. Presentation, tumor histology, stage at time of diagnosis, treatment, and outcome were recorded for all patients.
RESULTS
From the Section of Pediatric Surgery, Department of Surgical Oncology, M.D. Anderson Cancer Center and University of Texas Medical School at Houston, Houston, TX. Presented at the 25th Annual Meeting of the American Pediatric Surgical Association, Tucson, Arizona, May 14-17, 1994. Address reprint requests to Richard J. Andrassy, MD, Division of Pediatric Surgery, 6431 Fannin, Suite 6.264, Houston, TX 77030. Copyright © 1995 by W.B. Saunders Company 0022-3468/95/3002-0030503.00/0
Four of the patients were found to have benign cystosarcoma phyllodes, one had osteosarcoma, and one had metastatic histiocytic lymphoma. These patients were excluded from further review. One patient presented with adenocarcinoma, with features of signet ring histology. This patient had biopsies of several colonic polyps but had no evidence of invasive colon cancer. Pathological review could not exclude possible metastatic disease from an unknown primary colon cancer, although this would be a very unusual site of colon cancer metastasis. Nine patients had infiltrating ductal carcinoma, only one of whom had features suggestive of secretory (juvenile) breast cancer. One patient had infiltrating lobular carcinoma in addition to infiltrating ductal carcinoma. Of the five patients who had documentation of receptor status, estrogen receptors were positive in three patients and negative in two. Progesterone receptors were negative in all five patients. The age at time of presentation ranged from 13 to 19 years (mean, 16.2 years). Five patients were white, four were black, and one was Hispanic. No patient had a history of radiation exposure or previous malignancy. Patients with a family history of breast cancer included one with a positive maternal (premenopausal) history, two with maternal aunts with breast cancer, and one with a maternal great aunt with breast cancer. The time from onset of symptoms until diagnostic biopsy ranged from 1 to 13 months (mean, 3.7 months). The patients were staged according to the AJCC 2 staging system. Two had stage I tumors, four had stage IIA, two had
322
Journa/of Pediatric Surgery, Vo130, No 2 (February), 1995: pp 322-324
Copyright © 1995 by W.B. Saunders Company INDEX WORDS: Breast neoplasms, carcinoma, adolescence.
C
ARCINOMA of the breast is rare in children and adolescents. 1 Although conservative man-
B R E A S T C A N C E R IN A D O L E S C E N T
FEMALES
stage IliA, and two had stage IV. Treatment involved combinations of surgery, radiation therapy, and chemotherapy. One stage I patient (with bilateral breast cancer) died of a radiation-induced sarcoma after treatment; the other stage I patient is alive without disease 15 years later. The stage IIA patients had a five-year survival rate of 50%; all stage IIIA and stage IV patients died within 5 years of diagnosis. Five of the 10 patients presented within the last 10 years. Mammography failed to diagnose cancer in any of the four patients tested, including one with an 8-cm mass. DISCUSSION
Management of a breast mass in a child or adolescent can be difficult. The majority of such breast masses represent benign processes such as abscess, hematoma, cyst or fibroadenoma. 3-6 Several large studies examining breast biopsy findings in patients under 30 years of age showed few or no biopsies positive for breast cancer. 4-6 In two of the largest series, 5.6 no biopsy specimens from patients under 20 years of age were positive for carcinoma of the breast. This has led to a policy of conservative management of breast masses in young patients by many physicians. However, malignancies involving the breast can occur in children and adolescents. 1 Masses in the breasts of pediatric patients can represent metastases from primary lesions such as Hodgkin's and non-Hodgkin's lymphoma, neuroblastoma, and rhabdomyosarcoma. Results of several studies 3,7 suggest that metastatic lesions might be more common than primary lesions in the breast of pediatric patients. Because a breast mass may be the presenting symptom in such patients, biopsy of the mass may lead to early diagnosis of the primary lesion, before the occurrence of other symptoms. In addition, primary breast lesions such as rhabdomyosarcoma and malignant cystosarcoma phyllodes can occur in pediatric patients. 3,7 Although primary carcinoma of the breast is rare in children and adolescents, 74 such cases were found in the world literature. I The present study involves the largest single-institution series of primary breast cancer in adolescents. No risk factors clearly identifying the young patients at risk for malignant breast masses have been determined. Family history of breast cancer, 8 especially hereditary or familial breast cancer, might be a risk factor for early-onset breast cancer. Some investigators have suggested that breast cancer in the young (under age 35) patient may have a better, 1worsC 4~ or similar ~2 prognosis to that in older patients. In addition, patients who present with breast cancer at a
323
ADOLESCENT WITH BREAST MASS
I FOLLOW FOR NO MORE THAN ONE MONTH
I ATTEMPTED ASPIRATION
CLEAR, YELLOW, OR GREEN FLUID AND MASS DISAPPEARS
r
BLOODY OR NO FLUID, MASS NOT RESOLVED
I CONSIDER ULTRASOUND
REPEAT EXAM IN ONE MONTH TEACH BREAST SELF EXAM
l
FINE NEEDLE ASPIRATION BIOPSY
r
OPEN BIOPSY
I IF BIOPSY NEGATIVE, TEACH SELF EXAM
Fig 1.
Evaluation of the adolescent with a breast mass,
young age have an increased risk for the development of second malignancies, tl Because of the small number of patients who present during adolescence, the prognosis is not clear. Although in this study, mammography was not helpful in the diagnosis of breast cancer, recent larger studies 1345 have shown that although mammography might be less sensitive in detecting malignancies in younger patients than in older ones, it may be of some value. In addition, studies have shown that fineneedle aspiration of breast masses in young patients may be helpful in establishing the diagnosis. 15-17 Delays in diagnosis often occur in the adolescent with breast cancer because of hesitancy to perform operative biopsy. Although fine-needle aspiration biopsy is less sensitive than operative biopsy, it might be adequate for most patients. Because adenocarcinoma of the breast, although rare, does occur in adolescent patients, it must be considered in the differential diagnosis of breast masses in this age group. Although mammography may be helpful in some cases, appropriate evaluation may require biopsy. Fine-needle aspiration may be helpful in this setting. Because inappropriate evaluation can lead to a delay in diagnosis, thorough evaluation of breast masses in adolescents is essential. Our recommendations for evaluation are shown in Fig 1. In addition, because several patients in this and other series presented at late stages or with large tumors, adolescent females should be taught and encouraged to practice breast self-examination, and breast examination by a physician should be part of the routine physical examination. This is especially important for patients with a family history of breast cancer. ACKNOWLEDGMENT
The authors thank Catherine Cooksley and Vincent Guinee, MD, for identifyingthe patient population through a search of the data base maintainedby the Department of Patient Studies.
324
CORPRON ET AL
REFERENCES 1. Ashikari H, Jun MY, Farrow JH, et al: Breast carcinoma in children and adolescents. Clin Bull 7:55-62, 1977 2. Beahrs OH, Henson DE, Hattes RV, et al: American Joint Committee on Cancer. Manual for Staging of Cancer (ed 3). Philadelphia, PA, Lippincott, 1988, pp 145-150 3. Greydanus DE, Parks DS, Farrell EG: Breast disorders in children and adolescents. Pediatr Clin North Am 36:601-638, 1989 4. Palmer ML, Tsangaris TN: Breast biopsy in women 30 years old or less. Am J Surg 165:708-712, 1993 5. Ferguson CM, Powell RW: Breast masses in young women. Arch Surg 124:1338-1341, 1989 6. Seltzer MH, Skiles MS: Diseases of the breast in young women. Surg Gynecol Obstet 150:360-362, 1980 7. Rogers DA, Lobe TE, Rao BN, et al: Breast malignancy in children. J Pediatr Surg 29:48-51, 1994 8. Lynch HT, Watson P, Conway T, et al: Breast cancer family history as a risk factor for early onset breast cancer. Breast Cancer Res Treat 11:263-267, 1988 9. de las Rochefordiere A, Asselain B, Campana F, et al: Age as prognostic factor in premenopausal breast carcinoma. Lancet 341:1039-1043, 1993 10. Noyes RD, Spanos WJ, Montague ED: Breast cancer in women aged 30 and under. Cancer 49:1302-1307, 1982
11. Lee CG, McCormick B, Mazumdar M, et al: Infiltrating breast carcinoma in patients age 30 years and younger: Long-term outcome for life, relapse, and second primaly tumors. Int J Rad Oncol Biol Physiot 23:969-975, 1992 12. Muscolino G, Villani C, Bedini AV, et al: Young age is not an ominous prognostic factor in breast cancer patients. Tumori 73:233-235, 1987 13. deParedes ES, Marstellar LP, Eden BV: Breast cancers in women 35 years of age and younger: Mammographic findings. Radiology 177:117-119, 1990 14. Jeffries DO, Adler DD: Mammographic detection of breast cancer in women under the age of 35. Invest Radiol 25:67-71, 1990 15. Ashely S, Royle GT, Corder A, et al: Clinical, radiological and cytological diagnosis of breast cancer in young women. Br J Surg 76:835-837, 1989 16. Yelland A, Grahan MD, Tron PA, et al: Diagnosing breast carcinoma in young women. Br Med J 302:618-620, 1991 17. Gupta RK, Naran S, Buchanan A, et al: Fine-needle aspiration cytology of breast: Its impact on surgical practice with an emphasis on the diagnosis of breast abnormalities in young women. Diagn Cytopathol 4:206-209, 1988
Discus sion K West (Indianapolis, IN): The authors have delineated their almost-40-year experience with a rare problem, but serious problem. Sixty percent of their patients presented with stage I or II disease; however, there was a 70% mortality rate for this group. Additionally, they reinforced the fact that mammography in the adolescent patient is not helpful in differentiating between benign and malignant lesions. What lessons can we learn from this series? Since this covers 40 years, how has your adjunctive therapy changed during this time? You suggested that breast masses in the adolescent should be followed for only 1 month before a biopsy is performed. In other large studies it has been suggested that masses that are not changing should be followed for longer periods. Are there any characteristics that could be identified by ultrasound that could assist in determining the time of biopsy? Can you give us a summary of the progression of these lesions? Did they double in size over a brief period? For the five patients who presented in the last 10 years, has the prognosis improved? (One of your patients with a stage I lesion actually suc-
cunlbed to treatment complications, not the primary disease.) C.A. Cotpron (response): The options of modified mastectomy or segmental mastectomy must be discussed with every patient. Because it has been suggested that some of these patients might have an increased risk for the development of second breast cancers or second malignancies, minimizing radiation exposure may be preferable, and mastecomy with immediate reconstruction may be suggested. Again, this is an individualized decision for the patient and surgeon. Further recommendations for the clinician include suggesting that a very careful family history be taken in all of these patients. With respect to diagnostic modalities, although no large studies have been done in these young patients, our study and others suggest that mammography is not very helpful. Ultrasound examination of the breast may be more helpful, and it is helpful in localizing more suspicious areas for ultrasound-guided biopsy.