Contributed equally
The aim of the present study was to summarize the clinical characteristics of primary breast lymphoma (PBL) and evaluate its management approaches. A total of 29 patients newly diagnosed with PBL, and treated between April 2006 and May 2013, were analyzed retrospectively. The median survival follow-up time for all patients was 66.8 (range, 25.4–110.0) months. The results of the follow-up revealed 22 living lymphoma-free patients and 7 patients who had succumbed to PBL. Of the 7 deceased patients, 6 had succumbed to lymphoma and 1 to chemotherapy-associated hepatic failure. In total, 1 patient who presented with bilateral breast lymphoma developed left breast relapse following lumpectomy and chemotherapy, 2 patients developed a bone marrow relapse, 1 patient developed lung and mediastinal lymph node relapses, and 1 patient developed a skin relapse. The Kaplan-Meier estimator predicted 5-year overall survival and progression-free survival rates for all patients of 74.4 and 74.6%, respectively. PBL appears to be a rare disease with a good overall prognosis and low incidence of local relapse, following chemotherapy alone or in combination with other treatments. Further studies investigating the development of effective agents for use in treatment-resistant patients are required.
Primary breast lymphoma (PBL), a rare lymphoma subtype, was first described in 1959 (
Previously, the International Extranodal Lymphoma Study Group reported the largest retrospective series of 204 patients with PBL and concluded that the combination of limited surgery, anthracycline-containing chemotherapy, and involved-field radiotherapy produced the best outcome for PBL (
Ethical approval was obtained from the Independent Ethics Committee of Zhejiang Cancer Hospital (Hangzhou, China). A total of 29 patients (1 male and 28 female) newly diagnosed with PBL and treated between April 2006 and May 2013 were retrospectively evaluated. All records were considered valuable if there was available data on patient demographics, pathological diagnoses, tumor details, therapeutic outcomes and follow-ups.
The pretreatment workup included obtaining a complete patient history and conducting a physical examination, liver and renal biochemical analysis, complete blood cell count, bone marrow biopsy, and computed tomography of the chest, abdomen and pelvis. Staging classification was performed according to the Ann Arbor classification (
When data were available, the stage-modified international prognostic index (IPI) score was defined for each patient included in the study. This score was established by Miller
Following diagnosis of DLBCL using a core needle or surgery, chemotherapy alone or in combination with radiotherapy was administered. The chemotherapy consisted of between 4 and 6 cycles of treatment with cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or a CHOP-like regimen. Chemotherapy was administered with or without central nervous system (CNS) prophylaxis, consisting of intrathecal methotrexate or cytarabine. The radiotherapy consisted of treatment with between 15 and 25 site-directed radiotherapy sessions, of between 1.8 and 2.0 Gy/session (total, 30–46 Gy), in the month following the completion of the chemotherapy program. Rituximab was recommended for patients with primary breast DLBCL. For other PBL histological subtypes, treatment was confirmed by the multidisciplinary lymphoma team of Zhejiang Cancer Hospital. The efficacy of treatment was assessed according to the International Workshop to standardize response criteria for NHLs (
Follow-up was performed by the oncologic outpatient clinic, and patients or relatives were contacted by telephone. The final follow-up was in June 2015. SPSS (version 17.0; SPSS, Inc., Chicago, IL, USA) software was used for statistical analysis. Kaplan-Meier estimators were used to calculate the overall survival (OS) and progression-free survival (PFS) rates. OS was measured from the date of diagnosis to the date of death or final follow-up. PFS was defined as the length of time from the date of diagnosis to the date of initial disease progression or death. Survival curves were plotted using the Kaplan-Meier estimator and compared using the log-rank test. Univariate analysis was performed to determine prognostic factors. P<0.05 was considered to indicate a statistically significant difference and all P-values were two-tailed.
A total of 29 patients were analyzed retrospectively. The baseline characteristics are listed in
The first-line therapy administered is summarized in
The median follow-up time for all patients was 66.8 (range, 25.4–110.0) months. By the final follow-up session, 22 patients were alive without lymphoma and 7 patients had succumbed to PBL. A total of 6 patients succumbed to lymphoma-associated mortality, including 1 patient who developed progressive disease during chemotherapy, and 1 patient succumbed to chemotherapy-associated hepatic failure. Among the 5 patients who relapsed, 4 (80.0%) relapsed within the first two years. One patient who presented with bilateral breast involvement developed left breast relapse following lumpectomy and chemotherapy, 2 patients developed lymphoma of the bone marrow, 1 patient developed relapses of the lung and mediastinal lymph nodes, and 1 patient developed lymphoma of the skin. No patients developed relapses of the CNS. Kaplan-Meier estimator analysis predicted the 1-, 3- and 5-year PFS rates of all patients to be 89.7, 79.3 and 74.6%, respectively (
The patient with MZL, who received a lumpectomy and five cycles of treatment with CHOP, was alive and disease-free by the final follow-up session. Of the 2 patients with ALCL, the patient who received a lumpectomy, five cycles of treatment with CHOP and 36 Gy of radiotherapy (18 sessions/day at 2.0 Gy/session), succumbed to lung and mediastinal lymph node relapse after 26.6 months. The other patient, who received hyperfractionated cyclophosphamide, vincristine, Adriamycin and dexamethasone/1A alternating with high-dose methotrexate and cytarabine/1B was alive and disease-free by the final follow-up. Of the 2 patients with MCL, the patient who received a lumpectomy and six cycles of treatment with R-CHOP [rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2) and vincristine (1.4 mg/m2, to a maximum of 2 mg), administered intravenously on day 1 and 100 mg oral prednisone on days 1–5] succumbed to a relapse of the bone marrow after 57.9 months. The other patient, who received a lumpectomy alone was alive and disease-free by the final follow-up.
The value of various potential prognostic factors, including age, ECOG performance status at presentation, tumor size, laterality, LDH levels, Ann Arbor stage, adjusted IPI value, surgery, cycles of chemotherapy received (>4), administration of rituximab and administration of radiotherapy, in predicting PFS and OS were evaluated. The impact of the prognostic factors is listed in
Several collaborative investigations have been conducted to define the clinical characteristics of PBL and evaluate its management approaches (
Clinically, the results of the present study were consistent with the published literature; the typical presentation was with a solitary, unilateral breast lump by a female aged between 50 and 60 years old (
CNS relapse occurs in between 5 and 16% of patients with primary breast DLBCL (
None of the treatments used, including surgery, chemotherapy, radiotherapy and rituximab, were associated with OS and PFS rates (
PBL appears to be a rare disease and it is therefore difficult to characterize. However, the results of the present study suggest that the overall prognosis of patients with PBL is reasonable, and that the incidence of local relapse is low following chemotherapy alone or in combination with other treatments. Further studies into the development of effective agents for use in treatment-resistant patients are required.
Kaplan-Meier curve showing the OS and PFS rates of patients with primary breast lymphoma in the present study. OS, overall survival; PFS, progression-free survival.
Clinical characteristics of the 29 patients evaluated.
Characteristic | Patient no., % |
---|---|
Gender | |
Male | 1 (3.4) |
Female | 28 (96.6) |
Age, years | |
Median | 50 |
Range | 24–69 |
ECOG performance status at presentation | |
0 | 14 (48.3) |
1 | 15 (51.7) |
Laterality | |
Right | 12 (41.4) |
Left | 13 (44.8) |
Bilateral | 4 (13.8) |
Tumor size |
|
Median | 4 |
Range | 1–10 |
Nodal site involvement at diagnosis | |
None | 16 (55.2) |
Axillary | 11 (37.9) |
Supraclavicular + axillary | 2 (6.9) |
Pregnant at diagnosis | |
Yes | 0 (0.0) |
Lactating at diagnosis | |
Yes | 1 (3.4) |
No | 28 (96.6) |
Lactate dehydrogenase levels | |
Elevated | 8 (27.6) |
Wild-type | 21 (72.4) |
Presence of B-symptoms | |
Absent | 27 (93.1) |
Present | 2 (6.9) |
Ann Arbor stage | |
IE | 16 (55.2) |
IIE | 13 (44.8) |
Adjusted IPI | |
0 | 10 (34.5) |
1 | 11 (37.9) |
2 | 7 (24.1) |
3 | 1 (3.4) |
Pathological classification | |
DLBCL | 24 (82.8) |
ALCL | 2 (6.9) |
MZL | 2 (6.9) |
MCL | 1 (3.4) |
For bilateral cases, tumor size was measured as the larger value of the left and right breast diameters. ECOG, Eastern Cooperative Oncology Group; IPI, International Prognostic Index; DLBCL, diffuse large B-cell lymphoma; ALCL, anaplastic large cell lymphoma; MZL, marginal zone lymphoma; MCL, mantle cell lymphoma.
Summary of the first-line treatment administered.
Treatment type | Patient no., n (%) |
---|---|
Regime | |
Surgery alone | 2 (6.9) |
Chemotherapy alone | 3 (10.3) |
Radiation and chemotherapy | 5 (17.2) |
Surgery and chemotherapy | 11 (37.9) |
Surgery, chemotherapy, and radiation | 8 (27.6) |
Surgery (n=21) | |
Lumpectomy | 16 (76.2) |
Modified mastectomy |
5 (23.8) |
Chemotherapy |
|
Anthracycline | 27 (100.0) |
Rituximab | 11 (40.7) |
Cycle no. | |
<4 | 1 (3.7) |
4–6 | 23 (85.2) |
>6 | 3 (11.1) |
Radiation | |
Fields (n=13) | |
Breast only | 4 (30.8) |
Breast and regional lymph nodes | 9 (69.2) |
Radiation dose (Gy) | |
Median | 36 |
Range | 30–46 |
Initially misdiagnosed as carcinoma of the breast
4 patients receiving intrathecal chemotherapy.
Univariate analysis of the impact of various prognostic factors on the results of treatment.
5-year PFS | 5-year OS | |||
---|---|---|---|---|
Prognostic factor | Rate, % | P-value | Rate, % | P-value |
Age | 0.257 | 0.273 | ||
≥50 years | 65.2 | 85.1 | ||
<50 years | 85.7 | 65.2 | ||
ECOG performance status at presentation | 0.666 | 0.617 | ||
0 | 77.1 | 77.1 | ||
1 | 73.3 | 72.7 | ||
Tumor size | 0.812 | 0.886 | ||
≥4 cm | 72.0 | 72.0 | ||
<4 cm | 78.6 | 78.6 | ||
Laterality | 0.146 | 0.129 | ||
Bilateral | 50.0 | 50.0 | ||
Unilateral | 78.4 | 78.1 | ||
Lactate dehydrogenase levels | 0.281 | 0.309 | ||
Elevated | 60.0 | 60.0 | ||
Normal | 81.0 | 80.4 | ||
Ann Arbor stage | 0.084 | 0.071 | ||
IE | 85.9 | 85.6 | ||
IIE | 61.5 | 61.5 | ||
Adjusted IPI | 0.281 | 0.309 | ||
0–1 | 81.0 | 80.4 | ||
2–3 | 60.0 | 60.0 | ||
Surgery | 0.848 | 0.809 | ||
Yes | 74.7 | 74.2 | ||
No | 75.0 | 75.0 | ||
Cycles of chemotherapy | 0.398 | 0.437 | ||
>4 | 77.1 | 77.1 | ||
≤4 | 66.7 | 62.5 | ||
Rituximab administered | 0.426 | 0.354 | ||
Yes | 77.9 | 77.9 | ||
No | 68.8 | 68.2 | ||
Radiotherapy received | 0.379 | 0.397 | ||
Yes | 83.3 | 83.3 | ||
No | 68.0 | 67.6 |
PFS, progression-free survival; OS, overall survival; ECOG, Eastern Cooperative Oncology Group; IPI, International Prognostic Index.