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J Clin Oncol. 2010 December 1; 28(34): 5088–5096.
Published online 2010 October 25. doi:  10.1200/JCO.2010.29.5683
PMCID: PMC3018358

Long-Term Survival Among Patients With Hodgkin's Lymphoma Who Developed Breast Cancer: A Population-Based Study



The increased risk of breast cancer (BC) among women receiving chest radiotherapy for Hodgkin's lymphoma (HL) is well-established. However, there are no large population-based studies that describe overall survival (OS) and cause-specific survival (CSS) compared with women with first primary BC.


For 298 HL survivors who developed BC (HL-BC group) and 405,223 women with a first or only BC (BC-1 group), actuarial OS and CSS were compared, accounting for age, BC stage, hormone receptor status, sociodemographic status, radiation for HL, and other variables. All patients were derived from the population-based Surveillance, Epidemiology, and End Results program.


OS among patients with HL-BC was significantly inferior that of to patients with BC-1: 15-year OS was 48% versus 69% (P < .0001) for localized BC, and 33% versus 43% (P < .0001) for regional/distant BC. Patients with HL-BC had a significantly increased seven-fold risk (P < .0001) of death from other cancers (ie, not HL or BC) compared with patients with BC-1. Mortality from heart disease among patients with HL-BC with either localized or regional/distant disease was also significantly increased (hazard ratio = 2.22, P = .04; and hazard ratio = 4.28, P = .02, respectively) compared with patients with BC-1. Although 10-year BC-CSS was similar for patients with HL-BC and BC-1 with regional/distant disease, it was inferior for patients with localized BC (82% v 88%, respectively; P = .002).


Women with HL may survive a subsequent diagnosis of BC, only to experience significant excesses of death from other primary cancers and cardiac disease. Greater awareness of screening for cardiac disease and subsequent primary cancers in patients with HL-BC is warranted.


Hodgkin's lymphoma (HL) is a highly curable disease,1 though the excellent life expectancy is offset by late effects of successful radiotherapy and chemotherapy, particularly the development of second malignancies.25 Fifteen to 30 years after therapy, cumulative mortality due to all second primary cancers exceeds deaths resulting from HL.3,68 Breast cancer (BC) accounts for the largest absolute risk of second cancers among female survivors of HL,2 with increased risks documented in numerous reports.2,4,5,916 For women treated for HL at age 25 years with chest doses of ≥ 40 Gy, without alkylating agents, Travis et al12 estimated that the cumulative risk of BC by age 55 years is almost one in three. Despite these sobering statistics, few studies have addressed survival after BC diagnosis in women with HL.9,1722 Most investigations consist of single-institution series,17,18,20,21 based on relatively small numbers of patients (range, 25 to 65 patients), followed-up for a median of less than 10 years.1720 Although several investigations analyzed patient survival by BC stage,1719 no studies have simultaneously controlled for the effects of age, hormone receptor status, year of BC diagnosis, and radiotherapy for HL. The actuarial calculation of other causes of death, from either heart disease, which is known to be significantly increased after radiotherapy for HL,23,24 or from other cancers, has also not been taken into account, although several reports addressed overall survival (OS),9,2022 disease-free survival,17,20 and/or disease-specific survival.18,19,21

Within a cohort of 9,948 women with a first primary HL reported to population-based cancer registries comprising the Surveillance, Epidemiology, and End Results (SEER) program, we identified patients with a new primary BC diagnosis after HL (HL-BC group). We hypothesized that OS and BC cause-specific survival (CSS) of these patients would be worse than for women in the SEER database with a first or only primary BC diagnosis (BC-1 group) and would be impacted by sociodemographic status and race. We compared OS, BC-CSS, CSS from other cancers, and heart disease CSS between groups. Patient-related, treatment-associated, and cancer-related variables were also analyzed to assess their effect on survival outcomes.


Patient Database

From the US population-based SEER 9 (1973 to 2006) limited-use database,25 317 HL survivors were registered with an incident new primary BC. Fourteen were not actively followed-up by the SEER program, and in five others, BC stage was unavailable; the remaining 298 patients were included in our analyses. For the BC-1 comparison group, 405,223 women were analyzed. For both groups, women with unstaged BC or ductal carcinoma in situ were excluded, as were “death certificate only,” “autopsy only,” and cases without active follow-up. Women who developed additional ipsilateral or contralateral BCs after initial BC diagnosis were not excluded.

Of the 298 patients with HL-BC, 18 patients developed a second cancer before developing BC, including cervix (n = 7), thyroid (n = 5), vulva (n = 1), uterus (n = 1), lip (n = 1), lung (n = 1), bladder (n = 1), and non-Hodgkin's lymphoma (NHL, n = 1). At last follow-up, 12 of these 18 patients were alive, and six had died: three as a result of BC, one as a result of “miscellaneous cancer,” one as a result of “other cause of death,” and one as a result of sepsis.

HL stage was determined from SEER extent of disease fields (see Appendix, online only). BC was staged using the “SEER historic stage A” variable, categorized as limited (ie, confined to breast tissue, excluding T4 tumors), regional (ie, lymph node involvement and/or locally advanced tumors), or distant (ie, metastatic). Information about radiation fields, radiation dose, chemotherapy, or hormonal therapy is not available in the SEER database, though radiotherapy for HL usually includes thoracic radiation.

Statistical Analysis

Actuarial OS and CSS were calculated using the Kaplan-Meier method. “Any other cancer” CSS reflects death from any cancer other than BC or HL. Survival times were measured from date of BC diagnosis until date of death or last follow-up. For the BC-1 group, actuarial survival was calculated for randomly selected subsets of patients, matched to the HL-BC group for sociodemographic status, age, and year of BC diagnosis (described in the Appendix, online only). Cox regression was used to compare survival outcomes, controlling for covariates. All analyses were conducted using SAS 9.1.3 software (SAS Institute, Cary, NC). Kaplan-Meier curves were prepared using R


Patient and Tumor Characteristics

Patient and tumor characteristics at time of HL diagnosis, grouped by stage of subsequent BC, are outlined in Table 1. Seventy-three percent of patients received HL treatment before age 40 years, the time of greatest radiocarcinogenicity of the breast.16,27 Eighty percent of women younger than 40 years and 73% of all women received radiation for HL. More than 80% were diagnosed with HL before 1990.

Table 1.
Patient and Tumor Characteristics at Time of HL Diagnosis Among 298 Women Who Developed a Second Primary Breast Cancer

Table 2 outlines clinicopathologic features of patients with HL-BC and BC-1 at time of BC diagnosis. For patients with HL-BC, 187 (63%), 90 (30%), and 21 (7%) had localized, regional, and distant BC, respectively, with comparable percentages (60%, 34%, and 6%, respectively) for first primary BCs. Among women with HL-BC, 67% diagnosed before 1996 had localized disease versus 61% diagnosed from 1996 to 2006 (P = .33). Because only 21 patients with HL-BC had distant disease (Table 1), regional and distant subgroups were combined for subsequent analyses. Median latency between diagnoses of HL and BC was 15.2 years (range, 0.6 to 33.3 years) and 15.3 years (range, 0.3 to 32.0 years), respectively, for localized and regional/distant BC. Patients with HL-BC were significantly (P < .0002) younger than patients with BC-1 (median age, 45 and 61 years, respectively) and had a higher sociodemographic status (defined in Table 2).28 Only 28 patients with HL-BC were nonwhite, consistent with the more common occurrence of HL in whites. Exclusion of these patients from subsequent analyses did not impact results. A greater proportion of BC-1 patients had unknown tumor grade, and unknown estrogen receptor (ER) and progesterone receptor (PR) status. The latter finding reflects the fact that most (89%) patients with HL-BC were diagnosed after 1990, when SEER registries initiated collection of ER and PR data. Among patients with BC for whom hormonal status was reported, those with antecedent HL were significantly more likely to have ER-negative and PR-negative BC. Among patients with localized BC for whom grade was reported, those with antecedent HL were more likely to have poorly differentiated cancer (P = .02).

Table 2.
Patient and Tumor Characteristics at Time of Breast Cancer Diagnosis for Women With HL-BC and Women With BC-1

There was no significant difference in tumor size distribution between patients with HL-BC and BC-1 with localized disease (data not shown). For localized BC, patients in the HL-BC group were more likely to have undergone a complete mastectomy than those in the BC-1 group (66% v 38%; P < .0001) and less likely to have undergone radiotherapy (19% v 38%; P < .0001). Similar findings were observed among patients with HL-BC with regional/distant BC. Among patients with HL-BC having localized BC, 35% who underwent partial mastectomy did not receive breast radiation (70% of these patients had received prior radiation for HL), as compared with 22% of patients with BC-1 (P = .015).

Vital Status at Last Follow-Up and Cause of Death

Table 3 outlines vital status at last follow-up and causes of death. Of patients with HL-BC, 55%, 28%, 10%, and 7% were followed up less than 5, 5 to 9, 10 to 14, and ≥ 15 years after BC diagnosis. Comparable numbers in the BC-1 cohort were 40%, 26%, 16%, and 19%, respectively. Of patients with HL-BC, 109 (37%) were deceased, compared with 187,308 (46%) of patients with BC-1. Of 58 women with HL-BC having localized BC who died, comparable percentages died from BC (38%) and other cancers (34%), whereas no deaths were attributed to HL. Not surprisingly, of 51 deaths among women with HL-BC having regional/distant BC, most resulted from BC (59%), similar to 64% of deaths in the BC-1 group.

Table 3.
Vital Status at Last Follow-Up and Cause of Death: Women With HL-BC (n = 298) and Women With BC-1 (n = 405,223)

For 28 patients with HL-BC who died of other cancers, median latency from HL to BC was 12.6 years (range, 0.6 to 27 years). Twenty-two had received radiation for HL, diagnosed at age 13 to 75 years (median, 29 years). Causes of death were lung cancer (n = 8), NHL (n = 7), esophageal cancer (n = 1), colon cancer (n = 1), anal cancer (n = 1), sarcoma (n = 1), and “miscellaneous malignant cancer” (n = 9). Among the seven patients whose death was attributed to NHL, five patients died ≥ 5 years after HL diagnosis (≥ 10 years in four patients). Among the nine patients dying from miscellaneous malignant cancer, four patients had third primary cancers reported to the SEER program (metastatic carcinoid, metastatic lung cancer, sarcoma, and malignant meningioma) that could have accounted for their deaths. Among the 19 other patients for whom a specific cancer death was reported, 11 patients had a separate SEER case listing that matched the cause of death, whereas eight patients did not. Among these 11 patients, the median latency from diagnosis of HL to the third primary cancer was18 years (range, 5.2 to 31 years). Subsequent survival for these 11 patients was poor (median, 7 months; range, 2 months to 5.2 years).

Eight patients with HL-BC (10% of 83 cancer-related deaths) and 4,595 patients with BC-1 (4% of 106,208 cancer-related deaths) died as a result of lung/bronchial cancer; nine patients with HL-BC (11% of 83 cancer-related deaths) and 2,992 patients in the BC-1 group (3% of 106,208 cancer-related deaths) died as a result of miscellaneous malignant cancers. These differences between the HL-BC and BC-1 groups in the rates of deaths from lung/bronchial cancer and miscellaneous cancers are consistent with the known increased risk of solid tumors among HL survivors (see Discussion).

Survival of HL-BC Versus BC-1 Groups

Table 4 and Figures 1A through through1C1C summarize the actuarial OS, BC-CSS, and other cancer CSS probabilities of patients with HL-BC and BC-1, matched for age, year of BC diagnosis, and sociodemographic status. Table 4 shows P values and hazard ratios (HRs) derived from Cox models comparing survival. Adjusting for covariates, the HL-BC group had a significantly poorer OS. Patents in the HL-BC group having localized disease had a significantly two-fold increased mortality (P < .0001) from either BC or heart disease as compared with patients in the BC-1 group. Patients in the HL-BC group with regional/distant disease demonstrated a significantly increased four-fold relative mortality from heart disease, with a nonsignificant 30% excess risk of death resulting from BC. It is noteworthy that HL survivors with localized or regional/distant BC had approximately seven times the hazard of death from other cancers as compared with patients with BC-1. Patients with regional/distant disease had a 4.7-fold increased risk of death from causes other than cancer or heart disease (refer to Table 3 footnote).

Table 4.
Comparison of Actuarial Survival Probabilities: Women With HL-BC (n = 298) Versus Women With BC-1 (n = 405,223)
Fig 1.
Comparison of (A) overall survival, (B) survival without death from breast cancer, and (C) survival without death from any other cancer (ie, excluding Hodgkin's lymphoma [HL] and breast cancer) for women with first primary breast cancer (BC-1, solid lines) ...

Prognostic Factors Among HL Survivors With BC

Table 5 shows results of univariate and multivariate analyses of prognostic factors that could potentially impact OS or BC-CSS in patients with HL-BC. For OS, age at BC diagnosis was inversely related to survival (P = .0003 and P = .004, respectively, for women with either localized or regional/distant BC). ER negativity was an adverse prognostic factor for OS among women with distant/regional BC. For women with localized BC, lower sociodemographic status was an adverse predictor (P = .04) of BC-CSS. For women with regional/distant BC, radiation for HL (HR = 2.61; P = .03) and ER negativity (HR = 3.07; P = .02) were significant adverse risk factors for BC-CSS. No other tested variable was a statistically significant predictor for OS or CSS in the multivariate analyses.

Table 5.
Variables That Affect Outcome in Women With HL Who Develop BC


An important new finding in our study, based on 298 patients with HL-BC and 405,223 patients with BC-1, is the observation that HL survivors in the general population who develop BC, as compared with women with a first or only BC, are at a significantly increased seven-fold risk of death from other cancers. Moreover, these patients experience significantly elevated two- to four-fold greater risks of cardiac death. For the first time, to our knowledge, the OS and CSS beyond 10 years, as well as the influence of several clinicopathologic factors (ie, sociodemographic status) on survival outcomes, are evaluated among patients with HL who develop BC. We show that lower sociodemographic status adversely affects both BC-CSS (P = .04) and OS (P = .09) among women who develop localized BC after HL.

Whereas the increased risk of new primary cancers in patients with HL is well-established,2,6,7,22,29 few studies address the development of two or more cancers after HL2 or subsequent mortality due to these malignancies.6,7 To our knowledge, none have addressed cancer mortality among HL survivors who develop BC. In our study, deaths from third or high-order cancers occurred at sites for which significantly increased risks of second cancers have been reported.,2,4,22,2931 including NHL,2,4,5,22,31,32 cancers of lung,2,4,22,29,31,33 esophagus,2,4,30,31 colon,2,4,22,30,31 anus,30 soft tissue,2,4,30,31 and brain.2,30

HL survivors have a significantly increased three- to 10-fold risk of lung cancer,2,4,22,29,31,33 with associated risk factors including prior radiation, alkylating-agent chemotherapy (both with significant dose-responses), and smoking history.33,34 Virtually all lung cancers develop in HL survivors who smoke.33,34 Thoracic radiation and smoking history also significantly increase the risk of lung cancer after BC.35,36 Although it is possible that deaths resulting from metastatic BC were erroneously ascribed to lung cancer for either patients with HL-BC or BC-1, the reported rate of such misclassification is low.37 Without independent histopathologic review, unequivocal classification of incident lung cancer after BC is not possible.

HL survivors have a significantly increased five-fold to more than 20-fold risks of NHL, with excesses persisting for more than 15 years after HL.2,4,5,22,31,32 Although death attributed to NHL in our study could have represented misclassified HL, this type of error is less likely in patients with a lengthy interval between the two lymphoma diagnoses. Similarly, although women originally assigned a diagnosis of HL could have actually had NHL, this type of misclassification occurs in only approximately 2% of patients.32

Using an actuarial comparison, patients in the HL-BC group had a significantly increased two- to four-fold risk of death from heart disease as compared with patients in the BC-1 group. Although patients with either HL23 or BC38 are susceptible to treatment-related cardiac toxicities (attributable to radiation and/or anthracycline chemotherapy), HL survivors tend to receive these exposures at a considerably younger age. Moreover, compared with patients with BC, patients with HL are generally given higher anthracycline doses and are irradiated to larger cardiac volumes, albeit at lower doses.39 The higher risk of cardiac death after HL is also noteworthy in view of the common use of mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy during much of the study period (1970s to mid 1980s), after which doxorubicin, bleomycin, vinblastine, and dacarbazine (which includes cardiotoxic doxorubicin) became more widely used.40

Among women with localized BC, patients in the HL-BC group had a significantly increased two-fold risk of death resulting from BC as compared with patients in the BC-1 group, which may in part be due to an approximately two-fold (albeit nonsignificant) greater prevalence of contralateral BC (Table 3). However, contralateral BC explains only a small part of the inferior BC-CSS (Table 4), which may also reflect patient susceptibility or treatment-induced factors and/or limitations in treatment options for BC after HL. For example, HL survivors are less likely to receive anthracycline chemotherapy for BC.21 Moreover, our study and another investigation21 also showed that HL survivors are significantly less likely to receive breast-conserving surgery or radiotherapy for BC than patients with BC-1. We also found that HL survivors who underwent breast-conserving surgery were less likely to receive radiation, most likely due to prior chest radiation for HL.

BC after treatment for HL may also exhibit a different biology compared with de novo BC. In an analytic population-based study of BC after radiation for HL, archived paraffin-embedded tissues from 19 women were compared with de novo BC.41 BC after HL was characterized by a 4.2-fold increase (P = .16) in microsatellite alterations, reflecting widespread genomic instability.41 Moreover, loss of heterozygosity in several chromosomes were significantly greater among HL survivors versus those with de novo BC.41 In another series, BC after HL, as compared with de novo BC, had a gene expression profile characterized by high proliferation, more aggressive tumor type (in approximately 80% of HL survivors),42 and greater likelihood of chromosomal aberrations (unpublished work discussed in Broeks et al42). Another investigation showed no differences in germ-line mutations in the ataxia-telangiectasia gene between BC after HL and de novo BC.43

Because of the long follow-up in our study, we are able to report for the first time 15-year OS of HL survivors who develop BC. Two matched-pair analyses have also compared OS of HL survivors against women with a first or only BC,20,21 although with far fewer patients and less follow-up than in our study. One series analyzed 21 HL survivors and another evaluated 53 patients (of whom 35 patients had HL). In neither study was OS significantly different between HL survivors and those with de novo BC at time points of 5 to 10 years.20,21

Compared with women with first or only BC, HL survivors were relatively younger at time of BC diagnosis; diagnosed in relatively later decades, in part reflecting the typical latency period of ≥ 10 years required for radiation-associated solid tumors27; and had a higher sociodemographic status, which is known to be correlated with HL.44,45 BCs among HL survivors were significantly more likely to be characterized by pathologic features of poorer grade, ER negativity, and PR negativity. Whether the greater risk of ER- and PR-negative tumors in our study may somehow reflect chemotherapy-induced (specifically mechlorethamine, vincristine, procarbazine, and prednisone) ovarian ablation46,47 is not known. Yahalom et al17 compared the histologic features of 45 BCs in 37 patients previously treated for HL with those in 935 patients with first BC. Nuclear grade, histologic grade, lymphocytic reaction, and lymphatic invasion were similar between the two groups.

The primary strength of the current study is the large number of patients (> 400,000) including 298 with BC after HL. All patients were derived from population-based registries, with no selection biases and with long-term follow-up, strengthening the generalizability of our results. Weaknesses of the SEER database include lack of information about radiation dose and fields as well as whether or not patients received chemotherapy (or what agents they received), factors important in predicting BC risks in patients with HL.5,9,12,16 In addition, it should be recognized that even the initial course of radiotherapy is underreported in the SEER program.48 With respect to BC-CSS, the power to detect covariate effects was limited because only 52 patients with HL-BC died as a result of BC, the most common cause of death in these patients. There were also small numbers of deaths from other causes.

Nonetheless, our results underscore the importance of continuing to monitor HL survivors who develop BC for late cardiac complications23 and additional malignancies, as well as the need to counsel patients on preventive measures such as smoking cessation and healthy lifestyle modifications. Systematic lifelong follow-up is needed to examine the emergence of long-term toxicity and associated morbidity and mortality.49,50 Future research should be directed at examining the underlying cancer biology and etiology of treatment-induced cancers, as well as inherent and treatment-induced genetic susceptibility of HL survivors. Genetic susceptibility may not only impact risk of developing additional cancers, but also subsequent survival, and warrants careful investigation.


We thank Laura Brumbaugh for her editorial assistance.


Determination of Hodgkin's Lymphoma Stage

Before 1983, the extent of disease (EOD) was coded using one of three systems: “Thirteen-digit (expanded) site-specific EOD,” which included detailed information about the number of lymph node regions above and below the diaphragm, as well as extranodal sites; the “Two-digit site-specific EOD,” which coded for stage (I through IV); or the “Two-digit site nonspecific EOD,” which coded for local (stage I), regional (stage II), or distant (stages III and IV) stage. The “Four-digit EOD” used from 1983 to 1987 and “Ten-digit EOD” used after 1987 also coded for the Hodgkin's lymphoma (HL) stage.

The “Thirteen-digit (expanded) site-specific EOD” (103 patients in this study) did not explicitly code stage, and in patients with nodal involvement on both sides of the diaphragm, as well as extranodal site(s), it could not be determined whether their disease was stage III or IV. In seven patients with nodal regions above or below the diaphragm and one extranodal site (above or below the diaphragm, respectively), the stage could be II (if extranodal site associated with involved nodes) or IV (if extranodal site not associated with involved nodes), which could not be determined from the SEER database. The “Thirteen-digit (expanded) site-specific EOD” (before 1983) provided detailed information about clinical versus pathologic staging, whereas the “Four-digit EOD” (1983 to 1987) and “Ten-digit EOD” (1988 onward) did not. Seven patients had clinical stage I to II disease but pathologic stage III disease. Because of the complexities of the different EOD coding methods, patients with stage III or stage IV disease were grouped together.

The variable of HL stage was analyzed with respect to its affect on overall survival and cause-specific survival. In the analyses of HL stage on outcome, for patients who were assigned stage II or stage IV HL, separate analyses were performed in which these patients were assigned stage II HL and separate analyses were performed in which these patients were assigned stage IV HL. For patients who were assigned clinical stage I to II or pathologic stage III HL, separate analyses were performed in which these patients were assigned clinical stage I to II HL and separate analyses were performed in which these patients were assigned pathologic stage III HL. As a result, four different analyses were performed in which HL stage was analyzed, incorporating all combinations of assigned HL stage.

Calculation of Actuarial Survival of Patients With First or Only Breast Cancer Matched for Age, Year of Diagnosis, and Sociodemographic Status

For the actuarial Kaplan-Meier overall and cause-specific survivals of the first or only breast cancer (BC-1) group (shown in Table 4 and Figs 1A through through1C),1C), patients with BC-1 were matched to the HL survivors who developed new primary BC (HL-BC group) based on age of BC diagnosis, year of BC diagnosis, and sociodemographic status. The patients with BC-1 were grouped into strata of 13 5-year age groups, four 10-year BC diagnosis groups, and four sociodemographic quartiles. Thus there were a total of 208 strata (13 × 4 × 4 = 208). For the matching analyses, the ratio of patients with BC-1 to patients with HL-BC was 21:1 for localized BC (ie, 3,927 patients with BC-1 matched to 187 patients with HL-BC) and 39:1 for regional/distant BC (ie, 4,329 patients with BC-1 matched to 111 patients with HL-BC), which represented the largest ratios we could feasibly attain from the patients with BC-1. For each patient with HL-BC, we randomly selected the number of patients with BC-1 (listed above) from the appropriately matched stratum of patients in the BC-1 group. We then calculated the BC-1 Kaplan-Meier survival based on those randomly selected patients. In order to achieve stable and less varied survival estimates, this matching procedure was independently repeated 100 times, with each matched analysis randomly selecting patients from the entire BC-1 population by matched stratum. Therefore, the calculated Kaplan-Meier actuarial survivals represent an average of 100 matched survival curves.

Table A1.

Cox Multivariate Analysis of Breast Cancer Patients With Localized Disease

Breast Cancer CSS
Any Other Cancer CSS
Heart Disease CSS
Other Cause CSS
History of HL< .00012.822.17 to 3.66.0022.001.31 to 3.08< .00017.034.53 to to 4.65.31
Year of diagnosis< .00010.980.98 to 0.99< .00010.970.96 to 0.97.86< .00010.980.97 to 0.98.13
Age of diagnosis< .00011.071.07 to 1.07< .00011.011.01 to 1.01< .00011.051.05 to 1.05< .00011.131.13 to 1.13< .00011.111.10 to 1.11
ER negative< .00011.311.26 to 1.36< .00011.741.64 to
ER borderline/ unknown< .00011.191.12 to 1.27< .00011.461.29 to to 1.24
PR negative< .00011.131.09 to 1.17< .00011.481.39 to to
PR borderline/ unknown.
Radiation for breast cancer< .00010.850.84 to 0.87< .00010.920.89 to to 1.10< .00010.880.85 to 0.91< .00010.770.75 to 0.79
Sociodemographic status< .00011.0031.002 to 1.003< .00011.001.00 to 1.01.83< .00011.011.01 to 1.01.07
Race, other/ unknown< .00010.840.80 to 0.88.00060.870.80 to 0.94.0030.810.71 to 0.93< .00010.720.63 to 0.81.0020.880.80 to 0.92
Race, black< .00011.421.38 to 1.46< .00011.471.40 to 1.54< .00011.211.12 to 1.31< .00011.431.35 to 1.52< .00011.341.28 to 1.41

Abbreviations: OS, overall survival; CSS, cause-specific survival; HR, hazard ratio; HL, Hodgkin's lymphoma; ER, estrogen receptor; PR, progesterone receptor.

Table A2.

Cox Multivariate Analysis of Breast Cancer Patients With Regional or Distant Disease

Breast Cancer CSS
Any Other Cancer CSS
Heart Disease CSS
Other Cause CSS
History of HL< .00012.221.68 to 2.93.15< .00016.873.43 to to 13.27< .00014.712.24 to 9.88
Year of diagnosis.0070.9980.997 to 0.999.0060.9980.996 to 0.999.00021.011.01 to 1.02< .00010.990.98 to 0.99.12
Age of diagnosis< .00011.031.03 to 1.03< .00011.011.01 to 1.01< .00011.051.04 to 1.05< .00011.111.11 to 1.11< .00011.091.09 to 1.09
ER negative< .00011.501.45 to 1.55< .00011.741.64 to 1.86.00041.281.12 to
ER borderline/ unknown< .00011.351.27 to 1.44< .00011.601.54 to
PR negative< .00011.321.27 to 1.36< .00011.451.34 to
PR borderline/ unknown< .00011.201.12 to 1.28< .00011.471.42 to
Radiation for breast cancer< .00011.041.02 to 1.05< .00011.101.08 to 1.12.0031.091.03 to 1.15.32< .00010.860.83 to 0.90
Sociodemographic status< .00011.011.01 to 1.01< .00011.011.01 to 1.01< .00011.011.01 to 1.01< .00011.011.01 to 1.02.80
Race, other/ unknown.050.960.92 to 0.999.020.940.89 to to to 1.27
Race, black< .00011.451.42 to 1.48< .00011.431.40 to 1.47< .00011.361.25 to 1.49< .00011.531.43 to 1.64< .00011.421.34 to 1.51

Abbreviations: OS, overall survival; CSS, cause-specific survival; HR, hazard ratio; HL, Hodgkin's lymphoma; ER, estrogen receptor; PR, progesterone receptor.


Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


The author(s) indicated no potential conflicts of interest.


Conception and design: Michael T. Milano, Lois B. Travis

Collection and assembly of data: Michael T. Milano, Huilin Li, Mitchell H. Gail, Lois B. Travis

Data analysis and interpretation: Michael T. Milano, Huilin Li, Mitchell H. Gail, Louis S. Constine, Lois B. Travis

Manuscript writing: Michael T. Milano, Lois B. Travers

Final approval of manuscript: Michael T. Milano, Huilin Li, Mitchell H. Gail, Louis S. Constine, Lois B. Travers


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