Persistent breast pain 5 years after treatment of invasive breastcancer is largely unexplained by factorsassociated with treatment

Robin J. Bell & Penelope J. Robinson & Fathima Nazeem &

Mary Panjari & Pamela Fradkin & Max Schwarz &

Susan R. Davis

Received: 29 April 2013 /Accepted: 13 August 2013 /Published online: 23 August 2013# Springer Science+Business Media New York 2013

AbstractPurpose The aim of our study was to establish the prevalenceof breast pain persisting 5 years after the initial treatment ofbreast cancer (BC) and the relationship between those persis-tent symptoms and general well-being.Methods The study involved women fromVictoria, Australia,who had survived at least 5 years from diagnosis, remainedfree from recurrence or new BC and completed the fifthannual follow-up questionnaire. Analysis involved both mul-tivariable logistic and linear regression.Results Of 1,205 women, 45 % reported breast pain whichpersisted for at least 3 months following initial treatment, andof these, 80 % reported pain persisting for at least 5 years. Thefactor contributingmost to the likelihood of persistent breast painwas current lymphedema; however, a full multivariable modelexplained <10 % of the likelihood of breast pain persisting for5 years. The presence of breast pain at 5 years was associatedwith only a modest reduction in general well-being.Conclusions Breast pain persisting for at least 5 years aftertreatment for BC is common. As the pain is largelyunexplained by factors associated with the characteristics of

the cancer or its treatment, the contribution of patient expec-tations to persistent breast pain may be considerable.Implications for Cancer Survivors Where persistent pain oc-curs, referral for the management of pain and, where appro-priate, lymphedema is warranted.

Keywords Pain . Breast . Cancer . Treatment . Oncology

Introduction

Breast cancer (BC) is the most common non-skin cancer inAustralian women [1].Whilst there has been an increase in theincidence of BC over the last two decades, this has beenassociated with an appreciable decline in BC-specific mortal-ity [1]. Both of these trends have contributed to an increase inthe number of women living with BC in the community. Of allAustralian women alive at the end of 2006, it is estimated that1.4 % (144,000) have been diagnosed with BC.

BC survivors report a range of side effects from treatment;one of the most common is breast pain. Estimates of theprevalence of pain persisting following initial treatment rangefrom 23 to 51 % [2–4], clearly varying by the time sincediagnosis. The reporting of pain has also been associated withreduced well-being; however, the directionality of this associ-ation is not clear. Women with reduced well-being are morelikely to report pain [5, 6], and women with pain are morelikely to report reduced well-being [7]. Althoughmany reportsaddress the issue of “pain”, we considered referring to “dis-comfort” rather than “pain”, as women describe a range ofsensations, including numbness and tingling, which are notstrictly “pain”. However, for the purposes of consistency withprior publications, we have used the word pain throughout thismanuscript.

R. J. Bell (*) : P. J. Robinson : F. Nazeem :M. Panjari :P. Fradkin : S. R. DavisWomen’s Health Research Program, School of Public Health andPreventive Medicine, Monash University, 99 Commercial Road,Melbourne, Victoria 3004, Australiae-mail: robin.bell@monash.edu

M. SchwarzDepartment of Medicine, Central Clinical School, MonashUniversity, 99 Commercial Road, Melbourne, Victoria 3004,Australia

M. SchwarzAlfred Health, Commercial Road, Melbourne, Victoria 3004,Australia

J Cancer Surviv (2014) 8:1–8DOI 10.1007/s11764-013-0306-6

In this report, we discuss the prevalence of persistent breastpain, factors associated with the persistence of pain and theassociation of persistent pain with reduced well-being.

Methods

This study was carried out using the Bupa Health FoundationHealth and Wellbeing After Breast Cancer Study (Bupastudy). This is a large cohort study of Victorian women withtheir first diagnosis of invasive BC. Women were recruited tothe study between June 2004 and December 2006. Mostwomen were recruited through the Victorian Cancer Registry(VCR), and all recruits completed an enrolment questionnaire(EQ) within 12months of diagnosis. The recruitment has beendescribed in detail previously [8]. The average time fromdiagnosis to completion of the EQ was 0.8 years (5th and95th centiles being 0.2 and 1.1 years, respectively). Fivefollow-up questionnaires (FQs) were completed every12 months following completion of the EQ, such that the fifthFQ was completed on average 5.7 (5th and 95th centiles were5.0 and 6.7, respectively) years from diagnosis. A total of1,683 women completed the EQ. The study is being carriedout with the approval of the ethics Committee of the CancerCouncil of Victoria and the Human ethics Committee ofMonash University and has therefore been performed in ac-cordance with the ethical standards laid down in the 1964Declaration of Helsinki and its later amendments. All partic-ipants have provided written informed consent.

In each of the FQs, women were asked about recurrentdisease (either local or distant) and new primary BC. Theywere also asked about surgery since the previous question-naire including mastectomy (unilateral or bilateral), breastreconstruction, as well as radiotherapy, adjuvant chemothera-py and adjuvant endocrine therapies. Women who completedthe FQ5 but reported either a recurrence or new cancer in anyof the FQs were not included in this analysis, as their activedisease and its management may have contributed to thebreast pain they described in the FQ5.

In the FQ5, we included a series of questions about breastpain following initial treatment. The first question askedwomen if they had experienced any breast pain that persistedfor at least 3 months after their initial surgery. If womenanswered yes to this question, they were directed to a numberof subsequent questions about the nature and severity of thesymptoms, for which they were given a list of options fromwhich they could choose one or more. The options includedaching, shooting pain, tingling, numbness, burning, phantombreast and “other”. If they chose “other”, they were given theoption of describing what they had experienced. Based on thedescription they provided, if the symptom could bereclassified according to the listed options, this was done.Women who described breast pain which did not fit the listed

options were retained in the group called “other”. In terms ofdescribing how disabling their initial breast pain was, theywere given three options: a little, moderately or severely. Asonly one woman described her initial pain as severely dis-abling, the categories of moderate and severe were combined,so the initial pain was reported as either a little, or more than alittle, disabling. Women were also asked if they were referredto a Pain Clinic (this was defined in the questionnaire as aclinic dedicated to pain management or a doctor specialisingin pain management). Finally, they were asked about whetherthey were still experiencing the breast pain at the time ofcompletion of the FQ5 and, if so, the level of disabilityassociated with the pain. The options were a little, moderateand severe.

Well-being has been assessed in all of the follow-up ques-tionnaires, including the FQ5, using the Psychological Gen-eral Well-Being Index (PGWB). The PGWB is a 22-itemquestionnaire which refers to the previous month. The sixdomains of the PGWB which include anxiety, depressedmood, positive well-being, self-control, general health andvitality are created by summing the scores of groups of ques-tions. The individual domain scores can take values between 0and 15, 20 or 25, depending on the number of questionsincluded in the domain score. The domains are summed toprovide a total score, which can range between 0 and 110.Some of the questions are reverse scored, to allow a higherscore to be associated with better well-being for both thedomains and the total score. The PGWB has been shown tobe both valid and reliable and can be generalized to non-institutionalized adults aged 25 to 74 years [9].

Frequencies have been used to describe the data. Groupshave been compared using odds ratios (with confidence inter-vals) and the Nagelkerke R2 statistic as an indicator of theproportion of the outcome predicted by the model. Medians(with ranges) have been used to describe continuous variables,as much of the data are not normally distributed, and compar-ison of groups has been done using non-parametric tests. Alogistic regression analysis was used to model factors associ-ated with the presence of breast pain at FQ5. Factors wereentered sequentially into the model on the basis of theNagelkerke R2 statistic. For the analysis of PGWB, mediansand ranges were reported, as the data were not normallydistributed. The Kruskal–Wallis test was used to comparethe PGWB total and domain scores for the groups. Modellingwas performed using a linear regression approach, with theoutcome variable being the PGWB total score and the inde-pendent variable being presence of persistent breast symptomsyes/no. In the multivariable model, adjustment was made forage and “living alone”. As the PGWB data were not normallydistributed, a bootstrapping approach with 5,000 repetitionswas used to minimise the influence of outliers on the findings[10]. The analysis was performed using the Statistical Packagefor the Social Sciences (SPSS) version 20 (SPSS Australasia

2 J Cancer Surviv (2014) 8:1–8

Pty Ltd, North Sydney, Australia) and Stata version 11.2(Stata Corp, College Station, TX, USA).

Results

A total of 1,683 women completed the EQ, and 1,305 womencompleted the FQ5. Women did not complete FQ5 becausethey had died during the course of the study (122), theyelected to leave the study early (246) or were lost to follow-up (10).

Of the 1,305 women who completed the FQ5, 100 womenhad experienced either a loco-regional or distant recurrence, ora meta-chronous primary BC at some stage between FQ1 andFQ5. These women were not included in this analysis.

Of the remaining 1,205 women, 540 (44.8 %) reportedbreast pain lasting at least 3 months after their initial surgery.Of the 540, 205 (38.0 %) chose only one symptom, 195(36.1 %) chose two and the remaining women (140)(25.9 %), chose more than two symptoms. The symptomchosen most frequently was numbness (311/540 or 57.6 %),followed by aching (265/540, 49.1 %) and then shooting pain(205/540, 38.0 %).

In terms of how disabling the initial pain was, 160 (29.6 %)women reported that it was either moderate or severe; how-ever, only 31/540 (5.8 %) women were referred to a PainClinic. Women who reported that their pain was moderately/severely disabling were more likely to be referred to a PainClinic (2/159, 13.8 %) than women who reported their painwas only mildly disabling 9/379 (2.4 %) (chi-square 27.1,p <0.001).

The level of disability caused by the breast pain wasassociated with the symptom type. The proportions of womenreporting that the sensation was moderate/severely disablingwere highest for the categories of tingling (47.7 %), burningpain (45.2 %), phantom breast (44.4 %) and shooting pain(42.9 %), compared with aching (37.4 %) and numbness(32.2 %).

Of the 540 women who reported initial breast pain, 530answered the question about current pain, and 424/530(80.0 %) reported that they still had pain at the time ofcompletion of the FQ5. The characteristics of the women withcurrent breast pain compared with those who no longer hadpain, but all of whom had reported the presence of pain at least3 months from diagnosis, are shown in Table 1 (n =530).

Compared with women who had pain initially but in whomthe pain did not persist, women with pain persisting for at least5 years were slightly younger (53.7 years compared with56.0 years, p =0.03), more likely to be beyond stage 1 atdiagnosis (59.2 %>stage 1 compared with 46.6 %, p =0.02),more likely to have been treated with chemotherapy (59.9 %compared with 46.2 %, p =0.01), more likely to report lymph-edema at FQ5 (27.9 % compared with 13.2 %, p =0.002) and

more likely to have reported their initial pain as more than alittle disabling (32.1 % compared with 17.9 %, p =0.005).They were also more likely to have described the quality oftheir initial symptom as either aching (52.8 % compared with36.8 %, p =0.003) or numbness (60.1 % compared with48.1 %, p =0.03).

The results of the logistic regression analysis for currentbreast pain/no current breast pain outcome are presented inTable 2. The first factor entered into the model was thepresence of lymphedema at FQ5, followed by the achingquality of the original pain, the stage at diagnosis, age atdiagnosis and finally the severity of the original pain. Thesmall value of the Nagelkerke R2 statistic indicates that al-though all the factors included in the final model were justi-fiable from a statistical standpoint, the model explained only amodest amount (9.3 %) of the likelihood that a woman wouldreport persistent breast pain at the time of completion of FQ5.

The findings in relation to the PGWB for the total and theindividual domain scores for the women in the groups whodid, and did not, report current breast pain are shown inTable 1. There were differences which were statistically sig-nificant at the 5 % level in favour of the group without breastpain at FQ5 for the total score (median of 76 versus a medianof 82, p =0.02) and the domain scores of anxiety (median of18 versus a median of 19, p =0.02) and general health (me-dians of 10 in each group, p =0.03). From the linear regressionanalysis presented in Table 3, it can be seen that the presenceof current breast pain was significant in the univariate analysisfor the domains of anxiety and general health and close tosignificant for the total score.We then adjusted the analysis forother factors associated with PGWB total and domain scores(age and “living alone”). The variable “living alone” wasassociated with statistically lower scores for the total and mostof the domain scores with a difference of almost 5 units in thetotal PGWB score in favour of the group not living alone. Thevariable “age” was significant for the domain “generalhealth”, with the score for this domain being positively asso-ciated with age. After adjustment, the coefficient for thecurrent breast pain group was statistically significant for thedomains of anxiety, depression and general health, but wasstill just borderline significant at the 5 % level for the totalscore. As can be seen from the r2 values in Table 3, despitevariables in the model for the total PGWB and its domainsbeing statistically significant, the multivariable analysis onlyexplained a very small proportion of the variation in theseoutcomes.

Discussion

Persistence of breast pain after initial BC treatment is animportant problem. Of women who had survived for at least5 years and were free of recurrent or meta-chronous primary

J Cancer Surviv (2014) 8:1–8 3

Table 1 Characteristics of the women with current breast pain compared with those with no breast pain in FQ5

Breast pain (n =424) No breast pain (n=106) Total (n=540) OR (95 % CI) p value Nagelkerke R2

N (%) N (%) N (%)

Stage at diagnosis (from VCR data)

Stage 1 194 (46.6 %) 61 (59.2 %) 255 (49.1 %)

>Stage 1 222 (53.4 %) 42 (40.8 %) 264 (50.9 %) 1.66 (1.07, 2.58) 0.023 0.016

Tumour size (VCR)

≤20 mm 294 (69.3 %) 71 (67.0 %) 365 (68.9 %)

>20 mm 130 (30.7 %) 35 (33.0 %) 165 (31.1 %) 0.90 (0.57, 1.41) 0.639 0.001

Number of nodes removed (VCR)

≤5 127 (30.1 %) 33 (32.0 %) 160 (30.5 %)

>5 295 (69.9 %) 70 (68.0 %) 365 (69.5 %) 1.10 (0.69, 1.74) 0.701 0.000

Hormone receptor status (VCR)

HR +ve 351 (82.8 %) 86 (81.1 %) 437 (82.5 %) 1.00 (0.54, 1.85) 0.991 0.003

HR −ve 61 (14.4 %) 15 (14.2 %) 76 (14.3 %)

Surgery reported in EQ

Breast-conserving surgery 299 (70.7 %) 78 (74.3 %) 377 (71.4 %)

Mastectomy 124 (29.3 %) 27 (25.7 %) 151 (28.6 %) 1.20 (0.74, 1.95) 0.465 0.002

Radiotherapy by FQ1

Yes 329 (77.6 %) 84 (79.2 %) 413 (77.9 %) 0.91 (0.54, 1.53) 0.714 0.000

No 95 (22.4 %) 22 (20.8 %) 117 (22.1 %)

Chemotherapy by FQ1

Yes 254 (59.9 %) 49 (46.2 %) 303 (57.2 %) 1.74 (1.13, 2.67) 0.011 0.019

No 170 (40.1 %) 57 (53.8 %) 227 (42.8 %)

Lymphedema at FQ5

Yes 118 (27.9 %) 14 (13.2 %) 132 (25.0 %) 2.54 (1.39, 4.64) 0.002 0.032

No 305 (72.1 %) 92 (86.8 %) 397 (75.0 %)

Endocrine therapy at FQ5

None 281 (66.3 %) 76 (71.7 %) 357 (67.4 %) 0.004

Tamoxifen 44 (10.4 %) 10 (9.4 %) 54 (10.2 %) 1.19 (0.57, 2.47) 0.641

AI 99 (23.3 %) 20 (18.9 %) 119 (22.5 %) 1.34 (0.78, 2.31) 0.292

Endocrine therapy at FQ5

AI 99 (23.3 %) 20 (18.9 %) 119 (22.5 %) 1.31 (0.77, 2.24) 0.324 0.003

None/tamoxifen 325 (76.7 %) 86 (81.1 %) 411 (77.5 %)

Severity of initial pain (FQ5)

A little disabling 288 (67.9 %) 87 (82.1 %) 375 (70.8 %)

>A little disabling 136 (32.1 %) 19 (17.9 %) 155 (29.2 %) 2.16 (1.26, 3.70) 0.005 0.026

Quality of original symptom (FQ5)a

Aching 224 (52.8 %) 39 (36.8 %) 263 (49.6 %) 1.92 (1.24, 2.98) 0.003 0.026

Shooting pain 162 (38.2 %) 37 (34.9 %) 199 (37.5 %) 1.15 (0.74, 1.80) 0.530 0.001

Tingling 90 (21.2 %) 18 (17.0 %) 108 (20.4 %) 1.32 (0.75, 2.30) 0.333 0.003

Numbness 255 (60.1 %) 51 (48.1 %) 306 (57.7 %) 1.63 (1.06, 2.50) 0.026 0.015

Burning 48 (11.3 %) 14 (13.2 %) 62 (11.7 %) 0.84 (0.44, 1.59) 0.589 0.001

Phantom pain 37 (8.7 %) 6 (5.7 %) 43 (8.1 %) 1.59 (0.65, 3.88) 0.305 0.003

Other 71 (16.7 %) 15 (14.2 %) 86 (16.2 %)

Any surgery from FQ1–FQ5

Yes 39 (9.2 %) 6 (5.7 %) 45 (8.5 %) 1.69 (0.70, 4.10) 0.247 0.004

No 385 (90.8 %) 100 (94.3 %) 485 (91.5 %)

Education (EQ)

<Year 12 214 (50.5 %) 54 (50.9 %) 268 (50.6 %)

>Year 12 210 (49.5 %) 52 (49.1 %) 262 (49.4 %) 1.02 (0.67, 1.56) 0.931 0.000

4 J Cancer Surviv (2014) 8:1–8

BC, 44 % reported that they had breast pain, which lasted atleast 3 months from the time of their initial treatment, and ofthese, 80 % reported that the pain was still present 5 yearslater. Only a very small number of women had been referred toa specialised Pain Clinic for the management of their symp-tom, although the availability of such clinics is limited.

Although some factors were associated with persistentbreast pain, specifically the presence of lymphedema, thenature of the initial pain being an ache, being beyond stage1 at diagnosis, being younger at diagnosis and the severity ofthe original pain, none of these factors contributed more than amarginal level to the likelihood of persistence of pain. It wasof interest that persistence was not related to whether theinitial surgery was mastectomy or breast-conserving surgery,whether the number of nodes removed from the axilla wassmall or large or whether treatment included radiotherapy. Themost important factor related to persistent breast pain was theco-existence of lymphedema. Although not classically con-sidered associated with “pain” as such, lymphedema is fre-quently described as a “heaviness” or “tightness” which isunpleasant.

There is wide variation in what has been reported in rela-tion to the prevalence of breast pain after treatment for BC [2,3]. Factors which influence the estimated prevalence includethe nature of the sample of women studied, for examplewhether women having subsequent reconstructive surgeryare included [7], whereas another study excluded womenwho had undergone a breast reconstruction [11]. The timesince initial treatment has also ranged widely from as littleas 6 months [5] to as long as 17 years [2]. Some studies havebeen large and have involved recruitment from a national database [11], whereas others have been small having recruited

from a single institution [7]. There have also been a number ofapproaches to ascertaining the nature and severity of the breastsymptoms, including the use of a validated pain questionnaire[7, 12]. Others assessed the nature of the breast symptoms bypresenting women with a range of options, describing thequality as well as using visual analogue scales, to assessseverity[2, 7].

Breast pain following treatment for BC has been attributedto surgery, particularly mastectomy, compared with breast-conserving surgery [12]. Persistence of pain has also beenreported to be associated with younger age at diagnosis [2,11, 13]. A number of other risk factors such as radiotherapy[2] have been identified, although the contribution of each tothe likelihood of persistence is modest [14]. It is clear thatthere is no one simple mechanical issue which is the cause ofpersistent breast pain after treatment for BC. Although themost important single variable in our analysis was the pres-ence of lymphedema at the time that pain was assessed (FQ5),we have also shown that lymphedema is not a static phenom-enon [15]. Lymphedema which is present early can resolve,and lymphedema can present for the first time years after theinitial treatment.

One factor which has received recent attention, in terms ofchronic pain in BC survivors, is the aromatase inhibitor mus-culoskeletal syndrome [6]. This is a phenomenon which wasclearly reported by our study participants and an importantreason for both the discontinuation of aromatase inhibitors andthe switch from such treatment to treatment with tamoxifen[16]. However, there was no association between the reportingof current breast pain in FQ5 and the reported use of any oraladjuvant endocrine therapy and, specifically, the use of aro-matase inhibitors, in the same questionnaire.

Table 1 (continued)

Breast pain (n =424) No breast pain (n=106) Total (n=540) OR (95 % CI) p value Nagelkerke R2

N (%) N (%) N (%)

Living condition at FQ5

Alone 67 (15.8 %) 20 (18.9 %) 87 (16.4 %) 0.81 (0.47, 1.40) 0.447 0.002

With others 357 (84.2 %) 86 (81.1 %) 443 (83.6 %)

Median (range) Median (range) Median (range) Kruskal–Wallis p value Nagelkerke R2

Age at diagnosis (EQ) 53.7 (29.0, 81.8) 56.0 (32.7, 80.7) 54.3 (29.0, 81.8) 4.651 0.031 0.013

PGWB—anxiety FQ5 18 (1, 25) 19 (3, 25) 18 (1, 25) 5.913 0.015 0.014

PGWB—depressed mood FQ5 13 (0, 15) 13 (2, 15) 13 (0, 15) 3.160 0.075 0.011

PGWB—positive well-being FQ5 13 (0, 20) 13 (2, 20) 13 (0, 20) 2.996 0.083 0.011

PGWB—self-control FQ5 12 (0, 15) 13 (1, 15) 12 (0, 15) 1.612 0.204 0.003

PGWB—general health FQ5 10 (1, 15) 10 (1, 15) 10 (1, 15) 5.128 0.024 0.015

PGWB—vitality FQ5 11 (0, 19) 13 (0, 19) 12 (0, 19) 3.768 0.052 0.009

PGWB—total FQ5 76 (9, 106) 82 (19, 106) 77 (9, 106) 5.491 0.019 0.012

OR odds ratio, 95 % CI 95 % confidence interval; VCR Victorian Cancer RegistryaWomen could report more than one type of symptom so the total number of symptoms reported exceeds the number of women in the analysis

J Cancer Surviv (2014) 8:1–8 5

The suggestion has been made that patient pre-treatmentcharacteristics may affect likelihood of reporting post-operative pain. Most studies have examined this in the acutesetting, rather than in relation to persistent breast pain. How-ever, given that in our study most women with breast painafter 3 months still had pain after 5 years, the findings of theacute studies are highly relevant. Although we did not ask ourstudy participants about the presence of breast pain prior totheir original treatment, there is evidence that the presence of

pre-operative pain is associated with a higher likelihood ofreporting pain in the first post-operative week [17]. Bruceet al. [17] reported that having a higher level of pre-operative “psychological robustness” was associated with areduced likelihood of reporting pain in the immediate post-operative period. Katz et al. [18] found that the risk of clini-cally meaningful pain present between 2 and 30 days follow-ing surgery was associated with the level of pre-operativeanxiety. Another consideration is what is termed “response

Table 2 Steps in development of the logistic regression model for the outcome variable “breast pain at FQ5”

Factors in model Factor added into model n Nagelkerke R2 p value OR 95 % CI

Step 0 Lymphedema 0.032 0.002 2.542 1.394 4.638

Step 1 Lymphedema Original pain—aching 529 0.054 0.007 1.842 1.184 2.867

Lymphedema Original pain—severity 529 0.049 0.020 1.907 1.105 3.292

Lymphedema Chemotherapy at FQ1 529 0.052 0.009 1.774 1.151 2.736

Lymphedema >Stage 1 at diagnosis 518 0.043 0.035 1.606 1.033 2.498

Lymphedema Original pain—numbness 529 0.043 0.057 1.523 0.988 2.348

Lymphedema Age at diagnosis 529 0.047 0.023 0.976 0.955 0.997

Step 2 Lymphedema + original pain (aching) Original pain—severity 529 0.066 0.051 1.733 0.997 3.014

Lymphedema + original pain (aching) Chemotherapy at FQ1 529 0.076 0.006 1.848 1.192 2.863

Lymphedema + original pain (aching) >Stage 1 at diagnosis 518 0.070 0.027 1.653 1.058 2.584

Lymphedema + original pain (aching) Original pain—numbness 529 0.067 0.030 1.626 1.048 2.522

Lymphedema + original pain (aching) Age at diagnosis 529 0.066 0.039 0.977 0.956 0.999

Step 3 Lymphedema + original pain (aching) + >stage 1a Original pain—severity 518 0.081 0.059 1.571 0.980 3.001

Lymphedema + original pain (aching) + >stage 1 Chemotherapy at FQ1 518 0.077 0.106 1.582 0.907 2.792

Lymphedema + original pain (aching) + >stage 1 Original pain—numbness 518 0.076 0.133 1.413 0.900 2.220

Lymphedema + original pain (aching) + >stage 1 Age at diagnosis 518 0.082 0.042 0.977 0.956 0.999

Step 4 Lymphedema + original pain (aching) + >stage 1+ age at diagnosis

Original pain—severity 518 0.093 0.052 1.748 0.995 3.071

Lymphedema + original pain (aching) + >stage 1+ age at diagnosis

Chemotherapy at FQ1 518 0.084 0.359 1.326 0.726 2.421

Lymphedema + original pain (aching) + >stage 1+ age at diagnosis

Original pain—numbness 518 0.087 0.162 1.382 0.878 2.175

OR odds ratio, 95 % CI 95 % confidence intervala Although the actual value of Nagelkerke R2 was marginally greater for the variable chemotherapy compared with stage, stage was included in themodel as chemotherapy was likely a surrogate measure for stage

Table 3 Univariable and multivariable linear regression modelling using bootstrapping for the PGWB total and domain scores

Domain Univariable analysis Multivariable analysis (adjusted for age and “live alone”)

R2 Beta coefficient (95 % CI) p value R2 Beta coefficient (95 % CI) p value

PGWB anxiety 0.0088 −1.136 (−2.147,–0.038) 0.036 0.0189 −1.08 (−2.087,–0.007) 0.043

PGWB depressed mood 0.0066 −0.571 (−1.089, 0.013) 0.041 0.0228 −0.567 (−1.068, 0.012) 0.038

PGWB positive well-being 0.0066 −0.770 (−1.577, 0.042) 0.064 0.0242 −0.788 (−1.598, 0.047) 0.060

PGWB self-control 0.0017 −0.292 (−0.910, 0.314) 0.354 0.0077 −0.254 (−0.839, 0.397) 0.426

PGWB general health 0.0096 −0.676 (−1.280, −0.057) 0.032 0.0562 −0.782 (−1.369, −0.168) 0.010

PGWB vitality 0.0057 −0.746 (−1.617, 0.116) 0.090 0.0273 −0.705 (−1.559, 0.205) 0.113

PGWB total 0.0075 −3.77 (−7.64, 0.184) 0.057 0.0237 −3.76 (−7.521, 0.199) 0.057

95 % CI 95 % bias-corrected confidence intervals

6 J Cancer Surviv (2014) 8:1–8

expectancy”. Montgomery et al. found that both the level ofpre-surgery distress and the expectation of pain were associ-ated with post-surgery pain severity [19]. Both distress andresponse expectancy are likely associated with personalitycharacteristics, which are not easily amenable to change[19]. Apart from the presence of lymphedema, the factorswe identified as associated with persistent breast pain at5 years were not modifiable. It may therefore be useful forclinicians to consider that time spent discussing the concernsof the patient prior to treatment may be an investment inminimising the persistence of symptoms in the long term.Once it is evident that breast pain is persistent, the referral ofwomen so affected to clinics specialising in the managementof chronic pain, and where appropriate, the management oflymphedema, would be appropriate.

Not all studies have found a significant relationship be-tween the persistence of symptoms following treatment forBC and either anxiety or depression [4]. Janz et al. reportedthat the symptom of fatigue, rather than pain, had the greatestimpact on self-reported quality of life in women with BCassessed on average 7 months after treatment [20]. In ourparticipants assessed at least 5 years after treatment for BC,the presence of breast pain was associated with a lower levelof self-reported well-being. However, it is important to notethat as the magnitude of the impact of living alone on totalwell-being (nearly 5 units) was even greater than that of breastpain (<4 units in the adjusted model), the context in which thepatient is living is a major consideration in managing theirsymptoms . To further place in context our finding of adifference of 4 units in the PGWB score associated with thepresence of breast pain, we have previously observed a differ-ence of nearly 12 points in the total PGWB score in associa-tion with the presence of active disease (recurrence or newbreast cancer) 2 years from diagnosis [21].

Strengths of our study include the population-based meth-od of recruitment and the high rate of retention in the study.The fact that our recruitment was through our state-basedcancer registry and that we know that our participants aresimilar to all women diagnosed with invasive breast cancerin Victoria in terms of age, tumour characteristics and place ofresidence [8] means that our findings are generalizable. Onelimitation to the description of current breast pain was that itwas limited to women who reported breast pain persisting forat least 3 months following their initial surgery. This did notallow for someone who developed breast pain de novo someyears after their initial treatment when they were free ofsymptoms initially. It also meant that a woman who did notrecall and therefore report her early pain would not be includ-ed in the estimate of pain present 5 years later. Both of theseeffects would result in an underestimate of the prevalence ofpain at 5 years.

In conclusion, breast pain persisting for at least 3 monthsafter initial treatment for BC is common, and most women with

pain after 3 months will still have pain 5 years later. Given thatthe persistence of pain remained largely unexplained by factorsassociated with treatment, consideration should be given toaddressing pre-operative patient distress and expectations offuture pain. When persistent breast pain is identified, referralto a specialist for pain management and, where indicated, to alymphedema clinic would be appropriate.

Acknowledgments The authors wish to thank the study participantsand the members of our Study Advisory Group: Dr. Jacquie Chirgwin, A/Professor John Collins, Professor Graham Giles, Mr. Peter Gregory, Mr.Stewart Hart,Miss Suzanne Neil andMrs. AvisMcPhee. The authors alsowish to thank members of the research team of the Health and WellbeingAfter Breast Cancer study, without whose hard work this large cohortstudy would not be possible (Maria La China and Jo Bradbury). Finally,we thank Ms. Helen Farrugia, Director of Information Systems, andProfessor Graham Giles, Director of the Victorian Cancer Registry, fortheir ongoing support of this study.

This work was supported by the Bupa Health Foundation (previouslythe Medical Benefits Fund of Australia Limited Foundation) (to SRD andRJB), the National Health and Medical Research Council of Australia(grant nos. 219279 to SRD and RJB, 490938 to SRD, 1034977 to MP),Novartis Oncology Australia, the L.E.W. Carty Trust, the Jack and RobertSmorgon Families Foundation, Connie and Craig Kimberley and RoyMorgan Research (all to SRD and RJB). This research project was alsosupported by the Victorian Government through a Victorian CancerAgency Research Fellowship (to RJB). None of the funding agencieshad any role in determining study design; in the collection, analysis andinterpretation of data; in the writing of the manuscript or in the decision tosubmit the manuscript for publication.

Conflict of interest None of the authors consider that they have anyconflict of interest that could inappropriately influence or bias this work.

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