Summary
Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on pathology and outcome. A multicentre retrospective study was undertaken to determine prognostic factors and the incidence of central nervous system (CNS) relapses.
Data was retrospectively collected on patients from 8 US academic centres. Only patients with stage I/II disease (involvement of breast and localized lymph nodes) were included. Histologies apart from primary DLBCL were excluded.
Between 1992 and 2012, 76 patients met the eligibility criteria. Most patients (86%) received chemotherapy, and 69% received immunochemotherapy with rituximab; 65% received radiation therapy and 9% received prophylactic CNS chemotherapy. After a median follow-up of 4.5 years (range 0.6 – 20.6 years), the Kaplan-Meier estimated median progression-free survival was 10.4 years (95% confidence interval [CI] 5.8 – 14.9 years), and the median overall survival was 14.6 years (95% CI 10.2 – 19 years). Twelve patients (16%) had CNS relapse. A low stage-modified International Prognostic Index (IPI) was associated with longer overall survival. Rituximab use was not associated with a survival advantage.
Primary breast DLBCL has a high rate of CNS relapse. The stage-modified IPI score is associated with survival.
Keywords: lymphoma, DLBCL, breast, rituximab, CNS, leptomeningeal relapse
Introduction
Primary breast lymphoma (PBL) was first defined in 1972 as a malignant lymphoma involving the breast with no evidence of concurrent widespread disease (Wiseman and Liao 1972). According to this definition, PBL only includes stage IE or IIE disease as defined by the Ann Arbor staging system. This is a rare subtype of Non-Hodgkin lymphoma (NHL), representing approximately 2% of extranodal NHL (Freeman, et al 1972) and about 0.5% of all breast tumours (Wiseman and Liao 1972), with the most common subtype being diffuse large B-cell lymphoma (DLBCL). The typical presentation is of a painless unilateral breast mass. Mammography screening does not appear to increase the detection rate of this entity (Domchek, et al 2002).
Due to the low incidence of PBL, there is a paucity of data on the natural history of this entity as well as the optimal treatment approach. The majority of published data are retrospective and limited due to the inclusion of small number of cases, different histologies and stages, which makes interpretation difficult. Although significant strides have been made in the molecular classification of DLBCL into distinct subtypes with differences in prognosis (Alizadeh, et al 2000, Hans, et al 2004), little is known about the pathological and molecular features of PBL. The largest study to date, of 104 patients classifying primary breast DLBCL into germinal centre B-cell (GCB) and non-GCB types, did not report differences in outcomes between these groups (Aviles, et al 2012). Regarding therapy, only two prospective trials have been reported to date. The first was a pre-rituximab era trial that randomized 96 patients to chemotherapy, radiation therapy or both, with superior survival reported in the combination therapy group (Aviles, et al 2005). The second was a single-arm trial utilizing immunochemotherapy with rituximab plus chemotherapy in 32 patients, and survival was similar to historical controls (Aviles, et al 2007). An area of controversy in the literature is the rate of central nervous system (CNS) relapse, with reports suggesting that it may be higher in primary breast DLBCL. However, the true rate and the use of prophylactic therapy varied widely. Given that there are no large North American series of patients with primary breast DLBCL, a multicentre collaboration was initiated to assess the natural history of primary DLBCL in the pre- and post-rituximab eras with specific emphasis on the incidence of CNS relapse.
Patients and Methods
Data were collected on patients with primary breast DLBCL diagnosed between 1992 and 2012 from eight academic medical centres in the USA. Institutional review board approval was obtained at each site. Patients were identified through institutional databases and tumour registries. Patients with a confirmed histological diagnosis of DLBCL were eligible for inclusion. Cases with disseminated stage IV DLBCL with breast involvement were excluded to avoid confounding with other primary sites. Cases of transformed DLBCL from low-grade lymphoma were also excluded. Patients with ipsilateral regional lymph node involvement and bilateral breast involvement were included.
A study-specific data collection spreadsheet was completed for each case. This included demographics, tumour characteristics, results of diagnostic tests, treatments administered and clinical outcomes. All available data on relapse or death were also collected. Due to the retrospective nature of this study, staging procedures were not standardized, but the Ann Arbor system (Carbone, et al 1971) was applied and the stage-modified International Prognostic Index (IPI) score (Miller, et al 1998) was determined using all the available information. Available immunohistochemistry (IHC) performed on the diagnostic specimens was reported from each of the respective institutions and staining for BCL2, CD10, BCL6 and MUM1 was recorded as positive if more than 30% of the malignant cells were immunoreactive. Percentage KI67 expression in each specimen was also recorded.
Response was assessed after completion of planned initial therapy according to the International Working Group response criteria (Cheson, et al 1999). These response criteria were applied retrospectively for cases where the response was not explicitly available. Overall survival (OS) was calculated from the date of diagnosis to the date of death or last follow-up. Progression-free survival (PFS) was calculated from the date of diagnosis until the date of disease recurrence or death from any cause. OS and PFS were estimated according to the Kaplan Meier method and the rates in each subgroup were compared with use of the log-rank method. Prognostic factors with a log-rank of p <0.1 were considered for inclusion in a Cox proportional hazards model. For comparisons between more than two groups, the Mantel–Cox log-rank test was used. Correlations among potential prognostic factors were examined using the Fisher's exact test for 2 × 2 tables. Two-sided tests were used throughout and p values of <0.05 were considered statistically significant. Analyses were carried out using PASW Statistics (Version 20, IBM, New York, USA).
Results
Baseline characteristics
Seventy-six patients met the eligibility criteria for our study. The baseline characteristics are shown in Table I. Most patients were females (97%), the median age was 62 years (range 17-87) and 9% had a prior history of benign breast disease. None of the patients had previous history of breast carcinoma. The most common presentation was with a palpable mass (78%); 13% had the disease detected incidentally by mammography. Right breast involvement was more common than left (62% versus 37%), and the median tumour size was 3 cm. Three-quarters of the patients had a solitary mass; 64% had stage IE disease and 36% had stage IIE, and only 3% had B-symptoms. The majority of patients (72%) had a low stage-modified IPI score of zero or one, with 34% in the very good risk group (IPI zero). Among the 41 patients in whom immunohistochemistry was available, BCL2 was positive in 83%, CD10 was positive in 30%; BCL6 was positive in 92%; MUM1 was positive in 84% and the median Ki67 expression was 80% (range 10 - 95%).
Table I.
Baseline Characteristics (N = 76 patients)
| N | % | ||
|---|---|---|---|
| Age | Median | 62 years | |
| Range | 17-87 years | ||
| Sex | Female | 74 | 97 |
| History of prior breast lump or biopsy | 7 | 9 | |
| Presentation | Screening mammogram | 10 | 13 |
| Palpable mass | 59 | 78 | |
| Laterality | Right | 47 | 62 |
| Left | 28 | 37 | |
| Bilateral | 1 | 1 | |
| Tumour size | Median | 3 cm | |
| Range | 1-12 cm | ||
| Number of tumours | Single | 56 | 75 |
| Multiple | 17 | 22 | |
| B-symptoms present | 2 | 3 | |
| ECOG performance status | 0 | 38 | 50 |
| 1 | 20 | 26 | |
| ≥2 | 4 | 5 | |
| Stage | IE | 49 | 64 |
| IIE | 27 | 36 | |
| Adjusted IPI* | 0 | 25 | 34 |
| 1 | 29 | 38 | |
| 2 | 17 | 22 | |
| 3 | 4 | 5 | |
| 4 | 1 | 1 | |
Abbreviations: DLBCL: Diffuse Large B-Cell Lymphoma; ECOG: Eastern Cooperative Oncology Group; IPI: International Prognostic Index
Complete data was available for most but not all the cases; in the latter, each missing variable (usually LDH or ECOG performance status) were considered to be 0 points.
Treatment and response
The therapy administered is summarized in Table II. Most patients (86%) received chemotherapy, with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-like regimens being the most common (76%). Rituximab was added to chemotherapy in 62% of cases. Radiation therapy was employed in 63% of patients with a median dose of 40 Gy (range 30.6 - 60 Gy), and was the only treatment modality in 4 (8%) of those receiving it. Prophylactic CNS chemotherapy was administered in only 9 (12%) of patients - 8 received intrathecal methotrexate (with a range of 1-6 doses) and 1 received systemic high-dose methotrexate (for 8 doses). Among the 65 patients who were treated with chemotherapy, 91% had a complete response (CR), 5% had a partial response and 4% had progressive disease. Patients who achieved a CR after chemotherapy had a significantly longer survival; the median PFS was 10.4 years (95% confidence interval [CI] 7.1 - 13.7) for patients achieving a CR versus 0.4 years (95% CI 0 - 0.8), for those not achieving CR (log rank p < 0.001) and the median OS was 14.6 years (95% CI 10.2 - 19.0) for those achieving a CR versus 1.9 years (95% CI 0 - 4.0) for those who did not (log rank p = 0.001).
Table II.
Treatment administered
| Chemotherapy regimen administered | |
| CHOP | 55 (72%) |
| Hyper-CVAD | 3 (4%) |
| Other* | 4 (5%) |
| No chemotherapy | 11 (14%) |
| Rituximab administered | 47 (62%) |
| Radiation to the breast administered | 48 (63%) |
| CNS prophylaxis administered | 9 (12%) |
Abbreviations: CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone; CNS: Central Nervous System; CVAD: Cyclophosphamide, vincristine, doxorubicin, dexamethasone.
Other refers to non-anthracycline-based chemotherapy, such as CVP (cyclophosphamide, vincristine, prednisone).
Relapse and Survival
After a median follow-up of 4.5 years (range 0.6 – 20.6 years), the Kaplan-Meier estimated median PFS of all the patients was 10.4 years (95% CI 5.8 – 14.9 years) and the median OS was 14.6 years (95% CI 10.2 – 19 years), as shown in Figure 1. For all the patients, the 5-year PFS and 5-year OS were 66% (95% CI 55 - 78%) and 75% (95% CI 64 - 86%), respectively. In patients treated with CHOP-like chemotherapy, the 5-year PFS and OS were 67% (95% CI 55 - 79%) and 78% (95% CI 67 - 89%), respectively. Among the 28 patients who relapsed, 68% occurred within the first 2 years. A total of 10 (13%) breast relapses were observed (5 ipsilateral, 3 contralateral and 2 bilateral). CNS relapse occurred in 12 patients (16%), including one patient that received intrathecal CNS prophylaxis. There was no difference in the rate of CNS relapse in the patients who received prophylactic CNS chemotherapy versus those who did not. Leptomeningeal involvement was observed in 4 patients, brain parenchymal involvement in 6 and 2 had both. All CNS relapses occurred within the first 2.8 years from the time of diagnosis. The median time to CNS relapse was not reached. The characteristics of the patients with and without CNS relapse are shown in Table III.
Figure 1.
Kaplan-Meier survival curves showing (A) progression-free survival and (B) overall survival of primary breast diffuse large B-cell lymphoma patients.
Table III.
Characteristics of primary breast diffuse large B-cell lymphoma patients with central nervous system relapse. None of the variables listed were significantly different between the two groups
| Patients without CNS relapse N = 64 | Patients with CNS relapse N = 12 | |
|---|---|---|
| Stage IIE | 17 (27%) | 6 (50%) |
| LDH Elevated | 7 (11%) | 2 (17%) |
| Stage-modified IPI High (2-4) | 16 (25%) | 5 (42%) |
| Rituximab given | 17 (27%) | 9 (75%) |
| CNS prophylaxis given | 5 (8%) | 1 (8%) |
Abbreviations: CNS: Central Nervous System; IPI: International prognostic index; LDH: Lactate dehydrogenase.
Prognostic factors
The stage-modified IPI was associated with OS; the 5-year OS was 87% (95% CI 77 - 97%) in patients with a score of 0-1 versus 48% (95% CI 25 - 71%) with a score of 2-4 (log rank p < 0.001), as shown in Figure 2A. Patients with a stage-modified IPI of 0 had a 5-year OS of 91% (95% CI 79 - 100%) compared to all others who had a 5-year OS of 66% (95% CI 51 - 81%; log rank p = 0.003), as shown in Figure 2B. There was no difference in PFS and OS in patients with solitary versus multiple breast masses or between patients with tumours less than 7 cm versus more than 7 cm. As most patients received CHOP or CHOP-like chemotherapy, there was no difference in PFS or OS with regards to chemotherapy administration; the survival for chemotherapy-treated patients was similar to the survival for all patients. Neither radiation therapy nor use of rituximab was associated with any change in PFS or OS. A Cox proportional hazards model including stage-modified IPI, number of breast tumours, tumour size, chemotherapy treatment, radiation treatment and rituximab treatment was constructed and the stage-modified IPI remained the only statistically significant prognostic factor.
Figure 2.
Kaplan-Meier survival curves showing overall survival stratified by stage-modified international prognostic index (IPI).
Discussion
Several collaborative efforts have been undertaken to define the natural history and the optimal treatment approach of PBL. A summary of the largest studies is provided in Table IV (Aviles, et al 2005, Aviles, et al 2012, Jeanneret-Sozzi, et al 2008, Ryan, et al 2008, Yhim, et al 2010). Most of these studies employed the criteria of Wiseman and Liao (1972) to define PBL. This definition has been challenged by some authors because it was based on a small number of cases and emphasized an anatomic definition of the disease more reminiscent of solid tumours, rather than one based on lymphoma biology (Yhim, et al 2010). However, insufficient data exists to revise the definition of PBL to include systemic DLBCL with breast involvement because in most cases it is difficult or impossible to prove that the breast was the primary extranodal site. Therefore, we maintained the traditional definition of PBL in our study and focused on cases with involvement limited to the breast and the regional nodes.
Table IV.
Comparison of published reports of primary breast diffuse large B-cell lymphoma
| Reference Study type | N | Median follow-up (years) | EFS/DFS/PFS | OS | CNS relapse |
|---|---|---|---|---|---|
| Avilés et al. (2005) Prospective, single centre: Chemo vs RT vs ChemoRT | 96 | 13.8 | 83% (10-year EFS in chemoRT arm) | 76% (10-year OS in chemoRT arm) | 11% |
| Ryan et al. (2008) Retrospective, multicentre | 204 | 5.5 | 54% (5-year PFS) | 63% (5-year OS) | 5% |
| Jeanneret-Sozzi et al. (2008) Retrospective, multicentre | 51† | 1.8 | 36% (5-year DFS) | 42% (5-year OS) | 14% |
| Yhim et al. (2010)* Retrospective, multicentre | 49‡ | 3.5 | 65% (5-year DFS) | 74% (5-year OS) | 10% |
| Avilés et al. (2012)* Retrospective, single centre | 104 | 6.5 | 60% (5-year DFS) | 53% (5year OS) | NR |
| Avilés et al. (2007) Retrospective, single centre | 32 | 5.4 | 75% (3-year EFS) | 63% (3-year OS) | 0 |
| Current study* Retrospective, multicentre | 76 | 4.5 | 66% (5-year PFS) | 75% (5-year OS) | 16% |
Survival data presented for the 51 cases of high-grade lymphoma, because multiple histologies were included
Survival data presented for the 49 cases that met criteria for primary breast diffuse large B-cell lymphoma, because advanced stage cases were included
Included patients treated with rituximab
Abbreviations: CNS: Central Nervous System; DFS: Disease-Free Survival; EFS: Event-Free Survival; NR: Not Reported; OS: Overall Survival; PFS: Progression-free survival; RT: Radiation Therapy.
Clinically, our results were consistent with the published literature - the typical presentation was of a woman in her 5th or 6th decade with a solitary, unilateral, predominantly right-sided breast lump (Jeanneret-Sozzi, et al 2008, Jennings, et al 2007). Screening mammography appeared to have a minor role in detection and most patients presented with palpable tumours. We did not analyse the effect of surgical therapy because most of the patients in our study had biopsies only, without any further surgical treatment. A large meta-analysis demonstrated that radical surgery offered no benefit in this disease (Jennings, et al 2007).
The strongest prognostic factor in our study was the stage-modified IPI score, which is consistent with other reports (Ryan, et al 2008, Yhim, et al 2010). This score was established by Miller et al (1998) and gives one point each for age ≥ 60 years, stage II, increased serum lactate dehydrogenase and an Eastern Cooperative Oncology Group performance status 2 or higher. The study reported by Miller et al (1998) compared chemotherapy against chemotherapy and radiotherapy in localized (Stage I-II) intermediate and high-grade NHL. The 5-year OS in the Miller study (Miller et al 1998) was 82% in patients with a stage-modified IPI score of 0-1, 71% with a score of 2 and 48% with a score of 3. The stage-modified IPI appeared to produce an even greater separation in our study with 5-year OS rates of 87%, 60% and 25%, respectively, for scores of 0-1, 2 and 3. Moreover, the present study identified a very good risk group of patients with a stage-modified IPI score of zero, who had a 5-year OS of 91%.
None of the treatment variables analysed in this study - chemotherapy, radiotherapy or rituximab - was associated with differences in survival. However, as this was a retrospective, non-randomized comparison, and the reasons for choosing each modality of treatment was not known, we could not reliably assess the effect of treatment modality on survival. The only randomized comparison to date showed a significantly better survival for patients who received combined chemotherapy and radiation therapy compared to either modality alone (Aviles, et al 2005). In our patients the combination of radiation with chemotherapy prevented local breast recurrences. Although rituximab is now routinely added to chemotherapy in patients with DLBCL (Habermann, et al 2006), we were not able to demonstrate a difference in survival with rituximab use in the small cohort of analysed patients. No prospective randomized trials with rituximab use exists in this subtype of NHL, and the only other retrospective study that analysed the effect of rituximab also did not detect a survival difference (Yhim, et al 2010). Both studies included only a relatively small number of rituximab-treated patients and thus may be underpowered to reach this conclusion. However, a lack of benefit for the addition of rituximab to chemotherapy was also observed in a recent analysis of patients with DLBCL and skeletal involvement (Held, et al 2013), raising the possibility that some DLBCL subtypes may not benefit from rituximab use.
We observed a rate of CNS relapse of 16% (including parenchymal brain disease in two-thirds of these). Given that this study was retrospective with variable use of CNS prophylaxis, this rate might be underestimated, because patients at higher risk might be selected to receive prophylaxis. However, rates of CNS relapses in previous reports also range from 5% to 15% (see Table IV). This high CNS relapse rate is comparable to primary testicular DLBCL, which carries a rate of up to 15% at 10 years (Zucca, et al 2003). Only a few patients in the current study (12%) received CNS prophylactic chemotherapy, so the utility of prophylaxis in preventing CNS relapse could not be determined. However, due to the pattern of predominantly parenchymal brain relapses, we hypothesize that systemic CNS-active chemotherapy prophylaxis (such as high-dose methotrexate) might be preferable to intrathecal prophylaxis. A similar phenomen has been noted in patients with testicular DLBCL in whom parenchymal CNS relapses can occur, even in patients receiving intrathecal CNS prophylaxis (Guirguis, et al 2012), again suggesting that systemic CNS prophylaxis may be superior to intrathecal prophylaxis. Although it appeared that patients with stage IIE disease and higher IPI scores were more likely to develop CNS relapse (see Table III), these differences did not reach statistical significance, probably due to the small numbers.
In summary, this is the first large multicentre North-American collaborative study of primary breast DLBCL confirming a unique natural history of this disease with high rate of CNS relapse. Our results may help to guide the design of clinical trials in this disease - important questions remain on the role of rituximab and whether adequate CNS prophylaxis to all patients might eliminate CNS relapses.
Acknowledgments
Funding
National Institutes of Health [CA109335], Lymphoma Research Foundation, the Dwoskin and Recio Family Foundation grants to I.S.L.
Footnotes
Author contributions
PJH, ADZ and ISL designed the study. PJH, MPS, RT and ISL analysed the data. PJH and ISL wrote the manuscript. All authors contributed patients, collected data and approved the final version of the manuscript.
Author Disclosures
None
References
- Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J, Jr., Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–511. doi: 10.1038/35000501. [DOI] [PubMed] [Google Scholar]
- Aviles A, Delgado S, Nambo MJ, Neri N, Murillo E, Cleto S. Primary breast lymphoma: results of a controlled clinical trial. Oncology. 2005;69:256–260. doi: 10.1159/000088333. [DOI] [PubMed] [Google Scholar]
- Aviles A, Castaneda C, Neri N, Cleto S, Nambo MJ. Rituximab and dose dense chemotherapy in primary breast lymphoma. Haematologica. 2007;92:1147–1148. doi: 10.3324/haematol.10892. [DOI] [PubMed] [Google Scholar]
- Aviles A, Neri N, Nambo MJ. The role of genotype in 104 cases of diffuse large B-cell lymphoma primary of breast. Am J Clin Oncol. 2012;35:126–129. doi: 10.1097/COC.0b013e318209aa12. [DOI] [PubMed] [Google Scholar]
- Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res. 1971;31:1860–1861. [PubMed] [Google Scholar]
- Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244. doi: 10.1200/JCO.1999.17.4.1244. [DOI] [PubMed] [Google Scholar]
- Domchek SM, Hecht JL, Fleming MD, Pinkus GS, Canellos GP. Lymphomas of the breast: primary and secondary involvement. Cancer. 2002;94:6–13. doi: 10.1002/cncr.10163. [DOI] [PubMed] [Google Scholar]
- Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer. 1972;29:252–260. doi: 10.1002/1097-0142(197201)29:1<252::aid-cncr2820290138>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Guirguis HR, Cheung MC, Mahrous M, Piliotis E, Berinstein N, Imrie KR, Zhang L, Buckstein R. Impact of central nervous system (CNS) prophylaxis on the incidence and risk factors for CNS relapse in patients with diffuse large B-cell lymphoma treated in the rituximab era: a single centre experience and review of the literature. Br J Haematol. 2012;159:39–49. doi: 10.1111/j.1365-2141.2012.09247.x. [DOI] [PubMed] [Google Scholar]
- Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:3121–3127. doi: 10.1200/JCO.2005.05.1003. [DOI] [PubMed] [Google Scholar]
- Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103:275–282. doi: 10.1182/blood-2003-05-1545. [DOI] [PubMed] [Google Scholar]
- Held G, Zeynalova S, Murawski N, Ziepert M, Kempf B, Viardot A, Dreyling M, Hallek M, Witzens-Harig M, Fleckenstein J, Rube C, Zwick C, Glass B, Schmitz N, Pfreundschuh M. Impact of rituximab and radiotherapy on outcome of patients with aggressive B-cell lymphoma and skeletal involvement. J Clin Oncol. 2013;31:4115–4122. doi: 10.1200/JCO.2012.48.0467. [DOI] [PubMed] [Google Scholar]
- Jeanneret-Sozzi W, Taghian A, Epelbaum R, Poortmans P, Zwahlen D, Amsler B, Villette S, Belkacemi Y, Nguyen T, Scalliet P, Maingon P, Gutierrez C, Gastelblum P, Krengli M, Raad RA, Ozsahin M, Mirimanoff RO. Primary breast lymphoma: patient profile, outcome and prognostic factors. A multicentre Rare Cancer Network study. BMC Cancer. 2008;8:86. doi: 10.1186/1471-2407-8-86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jennings WC, Baker RS, Murray SS, Howard CA, Parker DE, Peabody LF, Vice HM, Sheehan WW, Broughan TA. Primary breast lymphoma: the role of mastectomy and the importance of lymph node status. Ann Surg. 2007;245:784–789. doi: 10.1097/01.sla.0000254418.90192.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998;339:21–26. doi: 10.1056/NEJM199807023390104. [DOI] [PubMed] [Google Scholar]
- Ryan G, Martinelli G, Kuper-Hommel M, Tsang R, Pruneri G, Yuen K, Roos D, Lennard A, Devizzi L, Crabb S, Hossfeld D, Pratt G, Dell'Olio M, Choo SP, Bociek RG, Radford J, Lade S, Gianni AM, Zucca E, Cavalli F, Seymour JF. Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group. Ann Oncol. 2008;19:233–241. doi: 10.1093/annonc/mdm471. [DOI] [PubMed] [Google Scholar]
- Wiseman C, Liao KT. Primary lymphoma of the breast. Cancer. 1972;29:1705–1712. doi: 10.1002/1097-0142(197206)29:6<1705::aid-cncr2820290640>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
- Yhim HY, Kang HJ, Choi YH, Kim SJ, Kim WS, Chae YS, Kim JS, Choi CW, Oh SY, Eom HS, Kim JA, Lee JH, Won JH, Shim H, Lee JJ, Sung HJ, Kim HJ, Lee DH, Suh C, Kwak JY. Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL) study. BMC Cancer. 2010;10:321. doi: 10.1186/1471-2407-10-321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zucca E, Conconi A, Mughal TI, Sarris AH, Seymour JF, Vitolo U, Klasa R, Ozsahin M, Mead GM, Gianni MA, Cortelazzo S, Ferreri AJ, Ambrosetti A, Martelli M, Thieblemont C, Moreno HG, Pinotti G, Martinelli G, Mozzana R, Grisanti S, Provencio M, Balzarotti M, Laveder F, Oltean G, Callea V, Roy P, Cavalli F, Gospodarowicz MK. Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group. J Clin Oncol. 2003;21:20–27. doi: 10.1200/JCO.2003.11.141. [DOI] [PubMed] [Google Scholar]