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Occult primary breast carcinoma presenting as axillary lymphadenopathy
The Breast (2002) 11, 414–418 r 2002 Elsevier Science Ltd. All rights reserved. doi:10.1054/brst.2002.0455, available online at http://www.idealibrary.com on
ORIGINAL ARTICLE
Occult primary breast carcinoma presenting as axillary lymphadenopathy Catherine Shannon, Geraldine Walsh, Francisco Sapunar, Roger A’Hern and Ian Smith Breast Unit, Royal Marsden Hospital, London, UK S U M M A R Y . Background: The objective of this study was to review the need for radiotherapy or not in patients with occult primary breast cancer presenting with axillary metastases treated with breast conservation usually with no surgery to the breast. Methods: From 1975 to 2001, 58 patients were treated with axillary lymphadenopathy from a cryptic primary breast carcinoma. After clinical and radiological assessment, 29 patients retained a diagnosis of occult primary breast carcinoma. Clinical and pathological data were collected retrospectively on the 29 patients and survival was calculated from the date of initial diagnosis using the Kaplan–Meier method. The median follow-up was 44 months. Results: Median age at diagnosis was 57 years (range 28–81 years). Sixteen patients had radiotherapy to the ipsilateral breast. Eleven patients received no local therapy to the ipsilateral breast and two patients had quadrantectomies which were negative for malignancy. Locoregional relapse occurred in 12.5% of patients who had received radiotherapy and 69% of those who had not received any radiotherapy (P = 0.02). Fifty-seven per cent of patients having a local relapse were salvaged with further surgery. The eventual breast conservation rate was 93%. Patients who received radiotherapy to the breast had significantly improved relapse-free survival (HR = 0.31; P = 0.04) and local relapse-free survival (HR = 0.09; P = 0.004). There were no significant differences in overall survival between those patients who had breast irradiation and those who did not (HR 0.91; 95% CI 0.18–4.5). Conclusion: Occult primary carcinoma with axillary metastases can be treated successfully with breast preservation but radiotherapy to the breast is necessary to minimize the risk of locoregional recurrence. r 2002 Elsevier Science Ltd. All rights reserved.
same series, around 50% of patients who received no form of breast treatment eventually had a breast recurrence.1,4, 9–11,14–18 Four series retrospectively compared mastectomy with breast irradiation in this group of patients and concluded that radiotherapy was as effective in terms of local control.2,15,18,19 In these small studies, there was no difference in survival between patients who underwent mastectomy and those who did not. We report on a series of patients presenting with axillary lymphadenopathy consistent with a histological diagnosis of occult primary breast cancer, all but 2 of whom had no surgery to the ipsilateral breast and some likewise had no breast radiotherapy. The objective of the study was to compare retrospectively local recurrence in patients who had radiotherapy to the ipsilateral breast with those who received no local breast radiotherapy or surgery. We also examined relapse-free and overall survival of the whole group.
INTRODUCTION Axillary metastases from clinically occult breast cancer represent a rare clinical entity first reported by Halsted in 1907.1 The presentation of isolated axillary lymphadenopathy without detectable tumour in the breast by either physical examination or mammography, represents between 0.3% and 0.8% of operable breast cancer.2–6 Previously reported series give an insight into the natural history of this presentation. In a combined analysis of 12 published series in which patients were treated with mastectomy, cancer was found in 69% of the breast specimens.2–5,7–13 In the Address correspondence to: Prof. Ian Smith, Breast Unit, Royal Marsden NHS Trust, Fulham Road, London SW3 6JJ, UK. Tel.: +44 (0)20 7808 2751; Fax: +44 (0)20 7352 5441; E-mail: [email protected] Received: 18 February 2002 Accepted: 14 May 2002
414
Occult primary breast carcinoma MATERIALS AND METHODS
Table 1
Patient characteristics
Characteristic
Patients were identified using the database of the Breast Unit of the Royal Marsden Hospital using the T0N1+ search criteria for the period 1975–2001. Patients with carcinoma in the axillary lymph nodes histologically consistent with breast carcinoma but without a clinically or mammographically detectable primary were included. Patients who had radiologically detectable primary in the breast or suspicious microcalcifications on mammography were excluded. Patients with a history of contralateral breast cancer or concurrent metastatic carcinoma of other origin were also excluded. More extensive investigations were performed at the discretion of the treating clinician. The survival rates were determined using the Kaplan– Meier estimates.20 Survival times were estimated from the date of diagnosis. Patients were censored at the time of last follow-up. Locoregional recurrence was defined as recurrence of disease in breast and/or regional lymph nodes. Cumulative risk of locoregional recurrence was estimated from the date of diagnosis. RESULTS Patient characteristics From 1975 to 2001, 58 patients with axillary lymph node metastases from a clinically occult breast primary were identified. Twenty-six patients (45%) were then found to have a primary breast carcinoma on radiological examination and thus excluded from this analysis. Two patients were excluded because they had a history of carcinoma of the contralateral breast and one because the patient had concurrent metastatic transitional cell carcinoma of the bladder. Clinical and pathological data were therefore collected on 29 eligible patients. All patients had mammography that failed to find a primary tumour in the breast. Seventeen patients had chest X-rays that were normal, eight patients had normal ultrasound scans of the liver, eight patients had normal bone scans and five patients had normal pelvic ultrasound scans. The median follow-up time was 44 months (range 2.5–257 months). The 29 patients had a median age of 57 years at diagnosis (range 28–81 years). Patient characteristics are shown in Table 1. The right axilla was the site of disease in 13 cases and the left axilla in 16 cases. Twenty-seven patients had no surgery to the breast as part of their initial treatment and two patients had a quadrantectomy that failed to show malignancy in the breast tissue. Nineteen patients had an axillary clearance as initial surgical treatment and 10 patients had surgical excision of the involved node only. Amongst the 19 patients having axillary clearance, there were a median of three
415
Local radiotherapy N = 16
No local radiotherapy N = 13
56.5 39–71
59 28–81
Surgery Axillary clearance Involved nodes only
11 5
8 5
Oestrogen receptor Positive Negative Unknown
7 4 5
4 2 7
Chemotherapy Yes No
11 5
5 8
Endocrine therapy Yes No
13 3
8 5
First site of relapse Locoregional Systemic
4 2 2
9 9 0
Breast conservation
16 (100%)
11 (85%)
Age (year) Median Range
involved nodes (range 1–25). Grading was possible in 15 patients: 13 (87%) had histologically grade 3 carcinoma and two patients had grade 2 carcinoma. Eleven tumours out of the 17 tested (65%) were positive for oestrogen receptors and six were negative. Treatment Sixteen patients had radiotherapy to the ipsilateral breast with 13 of these patients also receiving radiotherapy to the supraclavicular nodes and five also having radiotherapy to the involved axilla. The five patients, who received radiotherapy to the axilla had all had surgical resection of the involved node only. Thirteen patients did not receive any radiotherapy as part of their initial management and two of these had negative quadrantectomies as described above. These patients had a similar median age to those who received local radiotherapy (59 vs 57 years) (see Table 1). Twenty-one of the 29 patients received adjuvant tamoxifen with the remainder receiving no endocrine therapy. Sixteen patients had adjuvant chemotherapy following their surgery (14 with anthracycline-containing chemotherapy and five patients with cyclophosphamide, methotrexate and 5-fluorouracil).
Relapse Thirteen patients (45%) relapsed during the follow-up period at a median of 29 months from diagnosis (range
416
The Breast
3–95 months). Seven of the 13 patients (54%) receiving no breast radiotherapy relapsed in the ipsilateral breast compared with none of the 16 patients who received breast radiotherapy (P = 0.001). Four patients relapsed in locoregional lymph nodes; two in axillary nodes, one in the supraclavicular fossa and one in the infraclavicular fossa. One of the axillary recurrences and the infraclavicular recurrence occurred in patients who had received radiotherapy to the breast, axilla and supraclavicular fossa. The two other patients with nodal relapse had not received any radiotherapy as part of their treatment. Eleven of the 13 patients had locoregional relapse as the sole site of initial relapse. Locoregional recurrence rates were 12.5% vs 69% for patients receiving breast irradiation compared to those who did not (P = 0.02). Two patients had systemic disease alone at relapse.
(HR = 1.09; P = 0.99). The effect of the number of involved nodes on survival did not reach statistical significance in this series of patients. Likewise the numbers were too small to detect whether adjuvant systemic therapy significantly affected the risk of recurrence (HR = 0.57; P = 0.42). At the time of analysis, 20 patients are alive with no evidence of malignancy. Seven patients have died of metastatic disease and two patients are alive with metastatic disease. The observed median overall survival is 255 months with a 5-year survival of 88%. There are no statistically significant differences in overall survival between patients who did not have breast irradiation and those who did (HR 1.04 95% CI 0.21–5.1) (see Fig. 2).
Outcome following Relapse Relapse-free and overall survival The median relapse-free survival for the whole group was 41 months. Median relapse-free survival for those who received breast radiotherapy was 78 months compared to 26 months for those who did not (see Fig. 1). Five-year actuarial relapse-free survival is 69% for irradiated patients and 32% for non-irradiated (P = 0.04). Patients who received radiotherapy to the ipsilateral breast had significantly improved relapse-free survival (HR 0.31; 95% CI 0.09–1; P = 0.04) and local relapse-free survival (HR 0.09; 95% CI 0.012–0.74; P = 0.004). The extent of axillary surgery did not have an impact on local relapse-free survival (HR = 1.23; P = 0.77) or relapse-free survival
Fig. 1
The seven patients with local relapse in breast were treated with wide local excision and breast irradiation in five and mastectomy in two. Thus, the overall breast conservation rate in the whole series was 27/29 (93%). Three patients received chemotherapy following surgical excision of the local relapse and three received further endocrine therapy. Four of the seven (57%) patients who relapsed in the breast have continued free of disease with a median follow-up of 3.5 years since salvage surgery. Nine patients have developed systemic disease, two patients relapsed systemically in the first instance, the four patients who relapsed initially in locoregional lymph nodes all went on to develop systemic disease
Relapse-free survival according to whether the patient received radiotherapy to the ipsilateral breast.
Occult primary breast carcinoma
Fig. 2
417
Overall survival according to whether the patient received radiotherapy to the ipsilateral breast.
and three patients who had a recurrence in the breast subsequently developed distant metastases.
DISCUSSION Axillary nodal metastases without evidence of a primary tumour in the breast represent a rare but well-defined subset of breast cancer patients. This series confirms the feasibility of breast conservation in this group of patients but highlights the importance of breast irradiation in long-term local control. In this series, the number of locoregional relapses was significantly reduced by the addition of radiotherapy to the breast. This confirms the work of previous authors15,18 (see Table 2). Ellerbroek found that 54% of patients treated without irradiating the breast developed a local recurrence compared to 19% of those who had breast irradiation.15 In our series, locoregional recurrence occurred in 12.5% of those who had radiotherapy and 69% of those who did not (P = 0.02). All patients in this series had a negative mammogram but obviously a substantial proportion had an occult breast primary. The ability of mammography to identify occult primary breast cancers in patients presenting with axillary lymphadenopathy is poor with series ranging from 0% to 56%.21 Newer imaging techniques such as MR imaging can identify an occult primary breast cancer with a greater sensitivity in patients with isolated axillary metastases at presentation.22 Other investigators have found that patients with occult primary carcinoma with axillary metastases can be treated with preservation of the breast without a
Table 2 Similar series of patients with axillary lymphadenopathy from an occult primary breast carcinoma Author
N
LR without radiotherapy
LR with radiotherapy
P
5-year survival
Campana (1989)18 Ellerbroek (1990)15 Shannon (2002)
30
NA
36%
NA
76%
29
54%
19%
P=0.06
71.8%
29
69%
12%
P=0.02
88%
negative impact on survival.19,23 Series from MD Anderson and Memorial Sloan-Kettering have shown that patients receiving breast irradiation for occult primary breast tumours have equivalent survival to those having mastectomy.2,15,19 This study shows that patient’s overall survival does not seem to be affected by local radiotherapy but that irradiation of the breast has a significant impact on the risk of local relapse. The extent of axillary surgery did not have a significant impact on overall survival or locoregional relapse-free survival but our numbers were small and 50% of the patients who had only the involved nodes removed then had radiotherapy to the axilla. Previous studies have found that the most important determinant of survival was the number of involved nodes in the axilla.19,24 The number of patients in this study did not allow us to confirm the impact of the number of involved nodes on survival. Five-year actuarial survival rates after treatment for axillary metastases from occult breast cancer range from 57% to 80%.2,7,11,15,18 Several authors have found that the prognosis of patients presenting with occult primary
418
The Breast
breast tumours is better than that reported for stage II breast carcinoma.25–27 Five-year overall survival of the patients in this series is 88% for both patients who received radiotherapy and those who did not. Our findings confirm that aggressive surgical treatment is not necessary in the absence of a detectable primary within the breast, but radiotherapy to the breast is necessary to prevent the risk of breast and locoregional recurrence.
REFERENCES 1. Halsted W S. Results of radical operation for cure of carcinoma of breast. Ann Surg 1907; 46: 1–19. 2. Baron P L, Moor M P, Kinne D W et al. Occult breast cancer presenting with axillary metastases: updated management. Arch Surg 1990; 125: 210–214. 3. Fitts W T, Stiner G C, Enterline H T. Prognosis of occult carcinoma of the breast. Am J Surg 1963; 106: 460–466. 4. Haagensen C D. The diagnosis of breast carcinoma. In: Haagensen C D ed. Diseases of the Breast. Philadelphia: WB Saunders, 1971; 486. 5. Owen H W, Dockerty M B, Gray H K. Occult carcinoma of the breast. Surg Gynecol Obstet 1954; 98: 302. 6. Fourquet A, De La Rochefordiere A, Campana F. Occult primary cancer with axillary metastases. In: Harris J R, Hellman S, Henderson C I et al. eds. Breast Diseases, 2nd Edition. Philadelphia: JB Lippincott, 1991; 892–896. 7. Ashikari R, Rosen P P, Urban J A et al. Breast cancer presenting as an axillary mass. Ann Surg 1976; 183: 415–417. 8. Bhatia S K, Saclarides T J, Witt T R, Bonomi P D, Anderson K M, Economou S G. Hormone receptor studies in axillary metastases from occult breast cancers. Cancer 1987; 59: 1160–1172. 9. Feigenberg Z, Zer M, Dinstman M. Axillary metastases from an unknown primary source: a diagnostic and therapeutic approach. Isr J Med Sci 1976; 12: 1153. 10. Feuerman L, Attie J N, Rosenberg B. Carcinoma in axillary lymph nodes as an indicator of breast cancer. Surg Gynecol Obstet 1962; 115: 5–8. 11. Kemeny M M, Rivera D E, Teri J J et al. Occult primary adenocarcinoma with axillary metastases. Am J Surg 1986; 152: 43. 12. Patel J, Nemoto T, Rosner D et al. Axillary lymph node metastasis from an occult breast cancer. Cancer 1981; 47: 2923–2927.
13. Weigenberg H A, Stetten K. Extensive secondary axillary lymph node carcinoma without clinical evidence of primary breast lesion. Surgery 1951; 29: 217–221. 14. Atkins H, Wolff B. The malignant gland in the hospital. Guys Hospital Rep 1960;1: 109–110. 15. Ellerbroek N, Holmes F, Singletary E, Evans H, Oswald M, McNeese M. Treatment of patients with isolated axillary nodal metastases from an occult primary carcinoma consistent with breast origin. Cancer 1990; 66: 1461–1467. 16. Klopp C T. Metastatic cancer of axillary lymph node without a demonstrable primary lesion. Ann Surg 1950; 131: 437–440. 17. Van Ooijen B, Bontenbal M, Henzen-Logmans S C, Koper P C M. Axillary nodal metastases from an occult primary consistent with breast carcinoma. Br J Surg 1993; 80: 1299–1300. 18. Campana F, Fourquet A, Ashby M A, Sastre X, Jullien D, Schlienger P et al. Presentation of axillary lymphadenopathy without detectable breast primary (T0N1b breast cancer): experience at Institut Curie. Radiother Oncol 1989; 15: 321–325. 19. Vlastos G, Jean M E, Mirza A N, Mirza N Q, Kuerer H M, Ames F C et al. Feasibility of breast preservation in the treatment of occult primary carcinoma presenting with axillary metastases. Ann Surg Oncol 2001; 8(5): 425–431. 20. Kaplan E L, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481. 21. Solin L J. Special considerations. In: Fowbel B, Goodman R L, Glick J H, Rosato E F eds. Breast Cancer Treatment: a Comprehensive Guide to Management. St. Louis, Mo: MosbyYear Book. 1991: 523–528. 22. Orel S G, Weinstain S P, Schnall M D, Reynolds C A, Schuchter L M, Fraker D L, Solin L J. Breast MR imaging in patients with axillary node metastases and unknown primary malignancy. Radiology 1999; 212: 543–549. 23. Merson M, Andreola S, Galimberti V, Bufalino R, Marchini S, Veronesi U. Breast carcinoma presenting as axillary metastases without evidence of a primary tumor. Cancer 1992;70(2): 504–508. 24. Rosen PP, Kimmel M. Occult breast carcinoma presenting with axillary lymph node metastases: a follow-up study of 48 patients. Hum Pathol 1990;21: 518–521. 25. Say C S, Donegan W L. Invasive carcinoma of the breast: prognostic significance of tumour size and involved axillary lymph nodes. Cancer 1974; 34: 469–471. 26. Salvadori B, Greco M, Clemente C, De Lellis R, Delledonne V, Galluzzo D et al. Prognostic factors in operable breast cancer. Tumori 1983; 69: 477–484. 27. Valagussa P, Bonadonna G, Veronesi U. Patterns of relapse and survival in operable breast carcinoma with positive and negative axillary nodes. Tumori 1978; 64: 241–258.
ORIGINAL ARTICLE
Occult primary breast carcinoma presenting as axillary lymphadenopathy Catherine Shannon, Geraldine Walsh, Francisco Sapunar, Roger A’Hern and Ian Smith Breast Unit, Royal Marsden Hospital, London, UK S U M M A R Y . Background: The objective of this study was to review the need for radiotherapy or not in patients with occult primary breast cancer presenting with axillary metastases treated with breast conservation usually with no surgery to the breast. Methods: From 1975 to 2001, 58 patients were treated with axillary lymphadenopathy from a cryptic primary breast carcinoma. After clinical and radiological assessment, 29 patients retained a diagnosis of occult primary breast carcinoma. Clinical and pathological data were collected retrospectively on the 29 patients and survival was calculated from the date of initial diagnosis using the Kaplan–Meier method. The median follow-up was 44 months. Results: Median age at diagnosis was 57 years (range 28–81 years). Sixteen patients had radiotherapy to the ipsilateral breast. Eleven patients received no local therapy to the ipsilateral breast and two patients had quadrantectomies which were negative for malignancy. Locoregional relapse occurred in 12.5% of patients who had received radiotherapy and 69% of those who had not received any radiotherapy (P = 0.02). Fifty-seven per cent of patients having a local relapse were salvaged with further surgery. The eventual breast conservation rate was 93%. Patients who received radiotherapy to the breast had significantly improved relapse-free survival (HR = 0.31; P = 0.04) and local relapse-free survival (HR = 0.09; P = 0.004). There were no significant differences in overall survival between those patients who had breast irradiation and those who did not (HR 0.91; 95% CI 0.18–4.5). Conclusion: Occult primary carcinoma with axillary metastases can be treated successfully with breast preservation but radiotherapy to the breast is necessary to minimize the risk of locoregional recurrence. r 2002 Elsevier Science Ltd. All rights reserved.
same series, around 50% of patients who received no form of breast treatment eventually had a breast recurrence.1,4, 9–11,14–18 Four series retrospectively compared mastectomy with breast irradiation in this group of patients and concluded that radiotherapy was as effective in terms of local control.2,15,18,19 In these small studies, there was no difference in survival between patients who underwent mastectomy and those who did not. We report on a series of patients presenting with axillary lymphadenopathy consistent with a histological diagnosis of occult primary breast cancer, all but 2 of whom had no surgery to the ipsilateral breast and some likewise had no breast radiotherapy. The objective of the study was to compare retrospectively local recurrence in patients who had radiotherapy to the ipsilateral breast with those who received no local breast radiotherapy or surgery. We also examined relapse-free and overall survival of the whole group.
INTRODUCTION Axillary metastases from clinically occult breast cancer represent a rare clinical entity first reported by Halsted in 1907.1 The presentation of isolated axillary lymphadenopathy without detectable tumour in the breast by either physical examination or mammography, represents between 0.3% and 0.8% of operable breast cancer.2–6 Previously reported series give an insight into the natural history of this presentation. In a combined analysis of 12 published series in which patients were treated with mastectomy, cancer was found in 69% of the breast specimens.2–5,7–13 In the Address correspondence to: Prof. Ian Smith, Breast Unit, Royal Marsden NHS Trust, Fulham Road, London SW3 6JJ, UK. Tel.: +44 (0)20 7808 2751; Fax: +44 (0)20 7352 5441; E-mail: [email protected] Received: 18 February 2002 Accepted: 14 May 2002
414
Occult primary breast carcinoma MATERIALS AND METHODS
Table 1
Patient characteristics
Characteristic
Patients were identified using the database of the Breast Unit of the Royal Marsden Hospital using the T0N1+ search criteria for the period 1975–2001. Patients with carcinoma in the axillary lymph nodes histologically consistent with breast carcinoma but without a clinically or mammographically detectable primary were included. Patients who had radiologically detectable primary in the breast or suspicious microcalcifications on mammography were excluded. Patients with a history of contralateral breast cancer or concurrent metastatic carcinoma of other origin were also excluded. More extensive investigations were performed at the discretion of the treating clinician. The survival rates were determined using the Kaplan– Meier estimates.20 Survival times were estimated from the date of diagnosis. Patients were censored at the time of last follow-up. Locoregional recurrence was defined as recurrence of disease in breast and/or regional lymph nodes. Cumulative risk of locoregional recurrence was estimated from the date of diagnosis. RESULTS Patient characteristics From 1975 to 2001, 58 patients with axillary lymph node metastases from a clinically occult breast primary were identified. Twenty-six patients (45%) were then found to have a primary breast carcinoma on radiological examination and thus excluded from this analysis. Two patients were excluded because they had a history of carcinoma of the contralateral breast and one because the patient had concurrent metastatic transitional cell carcinoma of the bladder. Clinical and pathological data were therefore collected on 29 eligible patients. All patients had mammography that failed to find a primary tumour in the breast. Seventeen patients had chest X-rays that were normal, eight patients had normal ultrasound scans of the liver, eight patients had normal bone scans and five patients had normal pelvic ultrasound scans. The median follow-up time was 44 months (range 2.5–257 months). The 29 patients had a median age of 57 years at diagnosis (range 28–81 years). Patient characteristics are shown in Table 1. The right axilla was the site of disease in 13 cases and the left axilla in 16 cases. Twenty-seven patients had no surgery to the breast as part of their initial treatment and two patients had a quadrantectomy that failed to show malignancy in the breast tissue. Nineteen patients had an axillary clearance as initial surgical treatment and 10 patients had surgical excision of the involved node only. Amongst the 19 patients having axillary clearance, there were a median of three
415
Local radiotherapy N = 16
No local radiotherapy N = 13
56.5 39–71
59 28–81
Surgery Axillary clearance Involved nodes only
11 5
8 5
Oestrogen receptor Positive Negative Unknown
7 4 5
4 2 7
Chemotherapy Yes No
11 5
5 8
Endocrine therapy Yes No
13 3
8 5
First site of relapse Locoregional Systemic
4 2 2
9 9 0
Breast conservation
16 (100%)
11 (85%)
Age (year) Median Range
involved nodes (range 1–25). Grading was possible in 15 patients: 13 (87%) had histologically grade 3 carcinoma and two patients had grade 2 carcinoma. Eleven tumours out of the 17 tested (65%) were positive for oestrogen receptors and six were negative. Treatment Sixteen patients had radiotherapy to the ipsilateral breast with 13 of these patients also receiving radiotherapy to the supraclavicular nodes and five also having radiotherapy to the involved axilla. The five patients, who received radiotherapy to the axilla had all had surgical resection of the involved node only. Thirteen patients did not receive any radiotherapy as part of their initial management and two of these had negative quadrantectomies as described above. These patients had a similar median age to those who received local radiotherapy (59 vs 57 years) (see Table 1). Twenty-one of the 29 patients received adjuvant tamoxifen with the remainder receiving no endocrine therapy. Sixteen patients had adjuvant chemotherapy following their surgery (14 with anthracycline-containing chemotherapy and five patients with cyclophosphamide, methotrexate and 5-fluorouracil).
Relapse Thirteen patients (45%) relapsed during the follow-up period at a median of 29 months from diagnosis (range
416
The Breast
3–95 months). Seven of the 13 patients (54%) receiving no breast radiotherapy relapsed in the ipsilateral breast compared with none of the 16 patients who received breast radiotherapy (P = 0.001). Four patients relapsed in locoregional lymph nodes; two in axillary nodes, one in the supraclavicular fossa and one in the infraclavicular fossa. One of the axillary recurrences and the infraclavicular recurrence occurred in patients who had received radiotherapy to the breast, axilla and supraclavicular fossa. The two other patients with nodal relapse had not received any radiotherapy as part of their treatment. Eleven of the 13 patients had locoregional relapse as the sole site of initial relapse. Locoregional recurrence rates were 12.5% vs 69% for patients receiving breast irradiation compared to those who did not (P = 0.02). Two patients had systemic disease alone at relapse.
(HR = 1.09; P = 0.99). The effect of the number of involved nodes on survival did not reach statistical significance in this series of patients. Likewise the numbers were too small to detect whether adjuvant systemic therapy significantly affected the risk of recurrence (HR = 0.57; P = 0.42). At the time of analysis, 20 patients are alive with no evidence of malignancy. Seven patients have died of metastatic disease and two patients are alive with metastatic disease. The observed median overall survival is 255 months with a 5-year survival of 88%. There are no statistically significant differences in overall survival between patients who did not have breast irradiation and those who did (HR 1.04 95% CI 0.21–5.1) (see Fig. 2).
Outcome following Relapse Relapse-free and overall survival The median relapse-free survival for the whole group was 41 months. Median relapse-free survival for those who received breast radiotherapy was 78 months compared to 26 months for those who did not (see Fig. 1). Five-year actuarial relapse-free survival is 69% for irradiated patients and 32% for non-irradiated (P = 0.04). Patients who received radiotherapy to the ipsilateral breast had significantly improved relapse-free survival (HR 0.31; 95% CI 0.09–1; P = 0.04) and local relapse-free survival (HR 0.09; 95% CI 0.012–0.74; P = 0.004). The extent of axillary surgery did not have an impact on local relapse-free survival (HR = 1.23; P = 0.77) or relapse-free survival
Fig. 1
The seven patients with local relapse in breast were treated with wide local excision and breast irradiation in five and mastectomy in two. Thus, the overall breast conservation rate in the whole series was 27/29 (93%). Three patients received chemotherapy following surgical excision of the local relapse and three received further endocrine therapy. Four of the seven (57%) patients who relapsed in the breast have continued free of disease with a median follow-up of 3.5 years since salvage surgery. Nine patients have developed systemic disease, two patients relapsed systemically in the first instance, the four patients who relapsed initially in locoregional lymph nodes all went on to develop systemic disease
Relapse-free survival according to whether the patient received radiotherapy to the ipsilateral breast.
Occult primary breast carcinoma
Fig. 2
417
Overall survival according to whether the patient received radiotherapy to the ipsilateral breast.
and three patients who had a recurrence in the breast subsequently developed distant metastases.
DISCUSSION Axillary nodal metastases without evidence of a primary tumour in the breast represent a rare but well-defined subset of breast cancer patients. This series confirms the feasibility of breast conservation in this group of patients but highlights the importance of breast irradiation in long-term local control. In this series, the number of locoregional relapses was significantly reduced by the addition of radiotherapy to the breast. This confirms the work of previous authors15,18 (see Table 2). Ellerbroek found that 54% of patients treated without irradiating the breast developed a local recurrence compared to 19% of those who had breast irradiation.15 In our series, locoregional recurrence occurred in 12.5% of those who had radiotherapy and 69% of those who did not (P = 0.02). All patients in this series had a negative mammogram but obviously a substantial proportion had an occult breast primary. The ability of mammography to identify occult primary breast cancers in patients presenting with axillary lymphadenopathy is poor with series ranging from 0% to 56%.21 Newer imaging techniques such as MR imaging can identify an occult primary breast cancer with a greater sensitivity in patients with isolated axillary metastases at presentation.22 Other investigators have found that patients with occult primary carcinoma with axillary metastases can be treated with preservation of the breast without a
Table 2 Similar series of patients with axillary lymphadenopathy from an occult primary breast carcinoma Author
N
LR without radiotherapy
LR with radiotherapy
P
5-year survival
Campana (1989)18 Ellerbroek (1990)15 Shannon (2002)
30
NA
36%
NA
76%
29
54%
19%
P=0.06
71.8%
29
69%
12%
P=0.02
88%
negative impact on survival.19,23 Series from MD Anderson and Memorial Sloan-Kettering have shown that patients receiving breast irradiation for occult primary breast tumours have equivalent survival to those having mastectomy.2,15,19 This study shows that patient’s overall survival does not seem to be affected by local radiotherapy but that irradiation of the breast has a significant impact on the risk of local relapse. The extent of axillary surgery did not have a significant impact on overall survival or locoregional relapse-free survival but our numbers were small and 50% of the patients who had only the involved nodes removed then had radiotherapy to the axilla. Previous studies have found that the most important determinant of survival was the number of involved nodes in the axilla.19,24 The number of patients in this study did not allow us to confirm the impact of the number of involved nodes on survival. Five-year actuarial survival rates after treatment for axillary metastases from occult breast cancer range from 57% to 80%.2,7,11,15,18 Several authors have found that the prognosis of patients presenting with occult primary
418
The Breast
breast tumours is better than that reported for stage II breast carcinoma.25–27 Five-year overall survival of the patients in this series is 88% for both patients who received radiotherapy and those who did not. Our findings confirm that aggressive surgical treatment is not necessary in the absence of a detectable primary within the breast, but radiotherapy to the breast is necessary to prevent the risk of breast and locoregional recurrence.
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