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The Breast 18 (2009) 378–381

Contents lists avai

The Breast

journal homepage: www.elsevier .com/brst

Original article

Are males with early breast cancer treated differently from femaleswith early breast cancer in Australia and New Zealand?

Jim Wang a,d, James Kollias a,b,c,*, Claire Marsh a,d,*, Guy Maddern d,e

a National Breast Cancer Audit, Royal Australasian College of Surgeons, Australiab Section of Breast Surgery, Royal Australasian College of Surgeons, Australiac Breast Surgeons Society of Australia and New Zealandd ASERNIP-S, Royal Australasian College of Surgeons, PO Box 553, Stepney, South Australia 5069, Australiae Department of Surgery, University of Adelaide, Australia

a r t i c l e i n f o

Article history:Received 29 July 2009Received in revised form21 September 2009Accepted 22 September 2009

Keywords:Breast CancerMale Breast CancerMen’s healthEarly Breast CancerDisparities in treatment

* Corresponding authors at: ASERNIP-S, Royal AustPO Box 553, Stepney, South Australia 5069, Australiaþ61 8 8362 2077.

E-mail addresses: claire.marsh@surgeons.org,(J. Kollias).

0960-9776/$ – see front matter � 2009 Elsevier Ltd.doi:10.1016/j.breast.2009.09.015

a b s t r a c t

Breast cancer in males is much rare than in females so in practice, male breast cancer treatment is likelyto follow the guidelines developed for female breast cancer patients. The objective of this study is tocompare the characteristics and treatment pattern of male breast cancer patients with comparablesubgroups of female breast cancer patients using data submitted to the National Breast Cancer Audit.

This is a retrospective analysis of 151 male breast cancers diagnosed and treated between 2000 and2008. Most of the male early breast cancer cases in this group were symptomatic ones in men aged > 50years with one invasive tumour. There was a similar proportion of lymph node positive cancer amongmales and females, although male breast cancer was more likely to be unifocal (P¼ 0.007) and oestrogenreceptor positive (P¼ 0.001). Male breast cancer patients almost always underwent mastectomy anda significant proportion of them (11%) received no surgical treatment. There were no differences inaxillary surgery although males were more likely to undergo a level 2 axillary surgery and less likely tohave sentinel node biopsy. Male patients were significantly less likely to undergo radiotherapy,chemotherapy or hormonal therapy for oestrogen receptor positive tumours.Conclusion: While the female oriented treatment guidelines are available, male patients with earlybreast cancer received different surgical and adjuvant treatment from comparable females.

� 2009 Elsevier Ltd. All rights reserved.

Introduction

Breast cancer in males is much rarer than in females, accountingfor less than one in every hundred cases treated. The age-stand-ardised rate is 1 per 100,000 males over the 20-year period of1982–2002 with an increasing annual incidence from 43 cases in1983–1984 in 2002 in Australia.1 Due to the low incidence, noclinical guidelines have been specifically developed for males withbreast cancer, although some information is available on theNational Breast and Ovarian Cancer Centre (NBOCC) website(http://nbocc.org.au). In practice, male breast cancer treatmenttends to follow the guidelines developed for female breast cancerpatients.

ralasian College of Surgeons,. Tel.: þ61 8 8363 7513; fax:

jim.kollias@health.sa.gov.au

All rights reserved.

Some studies based on data synthesised from many smallerstudies concluded that male breast cancer is similar to breastcancer in females except that males are more likely to haveoestrogen- and progesterone receptor positive tumours.1,2 Otherreports have indicated significant differences in the biology andclinicopathologic characteristics between male and female breastcancer.3,4 A recent large review of male and female breast cancerpatients in a USA veteran population reported some differences inthe biology, pathology, presentation, ethnicity, and survivalbetween the sexes.5 It is likely that some differences between themale and female breast cancer are related to how and whenthe cancer is detected. Male breast cancer is often detected symp-tomatically, probably at a later stage, while a high proportion offemale breast cancer is detected through mammographic screeningwhen the tumour is small and at an early stage. Therefore it maybe appropriate to compare male breast cancer patients withsymptomatically detected female breast cancer patients, in partic-ular post-menopausal females. Similarly, comparison of treatmentpatterns of male and female breast cancer is only meaningful if it iscarried out between these two groups.

Table 1Patient and breast cancer characteristics in male breast cancer patients andcomparable female groups.

Male FG-1a P¼ FG-2a P¼

Age – mean (SD) 66.9(12.4)

58.3(14.6)

0.001 67.4(10.9)

0.649

% With one tumour 93% 79% 0.001 82% 0.007Oestrogen receptorþ 93% 73% 0.001 75% 0.001Progesterone receptorþ 79% 61% 0.001 59% 0.001LNþ 48% 46% 0.354 44% 0.204% Invasive tumour 94% 91% 0.095 91% 0.085N 151 12585 7235Invasive tumour cases onlyTumour size (mm)

– mean (SD)20.4(10.2)

24.7(18.1)

0.007 24.3(17.5)

0.011

Tumour histology grade 1 19% 18% 0.361 19% 0.5502 47% 42% 0.121 43% 0.2283 25% 35% 0.014 31% 0.097

Lymphovascularþ 31% 31% 0.803 27% 0.552N 139 11293 6739

a FG-1¼ symptomatically detected females, FG-2¼ post-menopausal symptom-atically detected females.

Table 2Surgical treatment in male breast cancer patients and comparable female groups.

Male FG-1a P FG-2a P

BCS 3% 50% 0.001 49% 0.001Mastectomy 86% 45% 0.001 45% 0.001No surgery 11% 5% 0.001 6% 0.001Axillary surgery 88% 87% 0.339 84% 0.111Sentinel Node Biopsy 25% 39% 0.001 36% 0.003Level 1 4% 6% 0.151 7% 0.091Level 2 53% 44% 0.016 42% 0.003Level 3 9% 9% 0.491 8% 0.442

a FG-1¼ symptomatically detected females, FG-2¼ post-menopausal symptom-atically detected females.

J. Wang et al. / The Breast 18 (2009) 378–381 379

The objective of this retrospective study is to compare thecharacteristics and treatment pattern of male breast cancerpatients with two subgroups of female breast cancer patients:symptomatic and post-menopausal symptomatic using datasubmitted to the National Breast Cancer Audit (NBCA).

Subjects and methods

The data for this study was obtained from the National BreastCancer Audit (NBCA). The audit database contains data on manyaspects of early breast cancer diagnosis and treatment. The NBCAuses the definition of early breast cancer as stated in the NBCCClinical Practice Guidelines for the Management of Early BreastCancer, namely, invasive tumours of not more than 5 cm in diam-eter with either impalpable or palpable but not fixed lymph nodesand with no evidence of distant metastases. This corresponds totumours that are T 1-2, N 0-1, and M0 (based on 1987 UICC clas-sification). Established in 1998, the NBCA comprised 68,949 patientepisodes on May 2008. A patient episode refers to one diagnosisand treatment process of a patient’s early breast cancer.

There were 151 male breast cancer records in the dataset,diagnosed and treated between 2000 and 2008. Ninety threepercent of the male patients in this series had symptomaticallydetected breast cancer. A small proportion of cases with missingkey data items were returned to the reporting surgeons for clari-fication and additional information. Any data items that remainedmissing after this process were not included in the analysis thatrequired the data. The variables used in the analysis were age atdiagnosis, invasive tumour size (mm), tumour grade (I, II, III), lymphnode positivity (where nodes were examined), oestrogen- andprogesterone receptor status (positive or negative) and number oftumours. Types of surgical treatment and adjuvant therapies wereused to determine treatment pattern.

Cancer pathology, surgical treatment, and adjuvant therapiesused to treat the male breast cancer patients were compared withthe female symptomatic breast cancer patients (female group 1,FG-1) and post-menopausal female symptomatic breast cancerpatients (female group 2, FG-2).

Statistical methodology

The characteristics of the breast cancer and treatment pattern inthe cohorts are expressed using mean and SD for continuous dataand proportion for categorical data. The two groups were analysedfor differences in the various diagnostic, pathological and surgicaltreatment parameters using the Chi-square test (or Fisher exact testwhere the number of cases is <5 in one cell) and ANOVA whereappropriate. A statistical significance level of P< 0.05 was used.Multivariate analysis using logistic regression was used to deter-mine the effect of age on the use of surgical treatment. The oddsratio and its 95% confidential interval from the analysis wereshown.

Results

Breast cancer characteristics

The age of the male breast cancer group ranged from 20 to 97years with a mean age 66.9 years, seventy percent of them aged�50 years. Most of the reported male cancer cases, 93%, had onetumour vs. around 80% with one tumour in the female groups(Table 1). Compared with FG-1 female group (symptomaticallydetected), the males were slightly older although they were aboutsame age compared with the FG-2 group (symptomatically detec-ted post-menopausal). The male breast cancer was more likely to

be oestrogen- and progesterone receptor positive than the femalebreast cancer. There was no difference between the males andfemales in proportion of LN positive tumours. For invasive cancercases only, the male breast cancer was smaller than the femalecases. There were no major differences in the presence of lym-phovascular (LV) positive tumours, and differences only betweenthe males and the FG-1 groups in histological grade 3.

Surgical treatment

Most male patients (86%) underwent mastectomy with onlyfour patients receiving breast conserving surgery (BSC). In contrast,less than half of the female patients underwent BCS. Males weretwice more likely to have no surgery. The proportion of malepatients who had axillary surgery, including sentinel node biopsy,levels 1–3 axillary surgery, was similar to the two females groupsalthough the males were more likely to undergo level 2 axillarysurgery and less likely to undergo sentinel node biopsy (Table 2).No male patient refused surgical treatment while 2% (FG-1) and 3%(FG-2) of female patients refused BCS, mastectomy or axillarysurgery.

Adjuvant therapies

Compared with the two female groups, the male patientswere almost always significantly less likely to undergo radio-therapy, chemotherapy or hormonal therapy for ERþ tumours.Their predominant form of hormonal therapy was Tamoxifen.Comparing only patients who underwent mastectomy, males

Table 3Adjuvant therapy use in male breast cancer patients and comparable female groups.

Male FG-1a P FG-2a P

Radiotherapy 44% 65% 0.001 60% 0.001Radiotherapy for

mastectomy patients45% 42% 0.231 36% 0.015

Chemotherapy 42% 53% 0.014 40% 0.231Chemotherapy for

mastectomy patients43% 60% 0.001 47% 0.082

Hormonal therapy inERþ patients

73% 80% 0.039 82% 0.021

Tamoxifen 72% 59% 0.001 51% 0.001

a FG-1¼ symptomatically detected females, FG-2¼ post-menopausal symptom-atically detected females.

J. Wang et al. / The Breast 18 (2009) 378–381380

were similar (vs. FG-1) or more (vs. FG-2) likely to receiveradiotherapy but less likely to receive chemotherapy (Table 3).Three male patients (2%) refused hormonal therapy while two(1%) refused chemotherapy, same as the female groups (1–2%)while slightly more female patients (5%) refused various therapy.Males aged �60 years were more likely to use Tamoxifen thanolder males (>60 years) (82% vs. 69%) but the difference was notsignificant (P¼ 0.167).

Discussion

The majority of the male breast cancer cases in this group aresymptomatic ones. This is consistent with the non-existence ofa screening program for men in Australia and New Zealand. Thestudy also found that most of the male breast cancer patients wereaged >50 years. Comparing to symptomatic male and femalepatients, especially post-menopausal females, males showeda similar proportion of LN positive cancer although male breastcancer was more likely to be unifocal and ERþ. While the tumoursize was smaller for male invasive cancer patients, there were nodifferences in tumour histological grade distribution or proportionof lymphovascular positive tumours.

Male breast cancer patients mostly underwent mastectomy buta significant proportion of them (11%) received no surgical treat-ment. There were no differences in the proportion of male andfemale patients receiving axillary surgery although males weremore likely to undergo a level 2 axillary surgery and less likely tohave sentinel node biopsy. Male patients were significantly lesslikely to undergo radiotherapy, chemotherapy or hormonal therapyfor ERþ tumours except the post menopause female breast cancerpatients also had a similar rate of chemotherapy.

Because breast cancer is uncommon in males, its diagnosistends to be delayed until it is symptomatically detectable, asmajority of the male breast cancers (93%) in this study, thetumour in male breast cancer patients may be at a moreadvanced stage at the time of diagnosis. In females aged 50–70years, less than half (42%) of the cases were detected symp-tomatically. This study showed that when males were comparedwith females with symptomatically detected breast cancer, theywere not different or even better in most prognostic parameters.A recent study comparing male and female breast cancerpatients, without distinguishing how the breast cancer wasdetected, showed a worse condition for male breast cancer in thebiology, pathology, presentation, ethnicity, and survival. Theauthors also suggested that the availability of mammographicscreening for females aged >50 years was the cause of thisdifference since a high proportion of female breast cancer isdetected at an earlier stage.5 On the other hand, since tumourstage, nodal status, tumour size and grade and hormone receptorstatus are more important prognostic factors in breast cancer, our

finding may suggest that both males and females with symp-tomatically detected breast cancer may have a similar long-termsurvival rate. As the NBCA is primarily a surgical audit it does notroutinely collect long-term survival data, however the NBCAdatabase is able to be linked with the AIHW National Death Indexto obtain survival data. The impact of differences found betweenmales and females with breast cancer on survival will beexplored in future publications.

Surgical treatment of male breast cancer is based on the sameprinciples as for females although the different views on theimportance of the breast coupled with the difficulty of carryingout BCS on small amounts of breast tissue may have lead to thedominant use of mastectomy as the surgical treatment in males.The axillary surgery pattern was also different between the malesand females although the overall rate was same. Breast cancers inmales tend to be slightly smaller than in females when they arefirst identified. While this study does not explore the reasons forthe differences in axillary surgery type between males andfemales, male anatomic factors, such as paucity of breast tissueand close tumour proximity to skin and nipple, facilitate dermallymphatic spread and early regional and distant metastasis.6 Thismay explain the tendency for males to receive more aggressiveaxillary procedures The extent of spread beyond the breast is oneof the most important factors in the prognosis (outlook) ofa breast cancer and should determine the use of axillary surgeryfor cancer treatment.

It is notable that males were twice more likely to receive nosurgical treatment. The NBCA collects one data item on refusal oftreatment, however as noted no males in this series refused anysurgical treatment so patient preference does not seem to explainthis difference. The NBCA does not collect any further informationregarding the reasons for treatment decisions. Under comparableconditions, such as disease, age and access to health care, it is foundthat males are less likely to seek treatment.7,8 We can speculate thatwhile the majority of males had a mastectomy, perhaps among theremaining proportion neoadjuvant therapies alone were consid-ered the recommended treatment due to other significant co-morbidities or unsuitability for anaesthesia. This may be supportedby the facts that males were more likely to be receptor positive, andso candidates for hormonal therapies.

It is expected that male patients are treated similarly tofemales with respect to the use of adjuvant therapies followingthe initial surgery. An earlier report by Macdonald et al. sug-gested that breast cancer is usually more advanced locally inmales so adjuvant radiotherapy are delivered proportionallymore frequently to males with breast cancer than to females.9

However, our results showed that overall the males were alwaysless likely to receive adjuvant therapy, including radiotherapy,than females. There was no difference for the patients whounderwent mastectomy, although males were still significantlyless likely to receive chemotherapy. The role for adjuvantchemotherapy in males is less well established, but existingevidence does suggest a benefit.10 The use of hormonal therapy isgenerally accepted as the standard care for ERþ male breastcancer based on its significant effect on survival rates in females2

and outcomes from several retrospective studies in males.11–13

Our study showed that three quarters of the male patients withhormone receptor positive tumours used hormonal therapy,almost all Tamoxifen. The reasons for a quarter of ERþ malepatients not receiving hormonal therapy are not clear. Althoughthe known side effects including loss of sexual desire, erectiledysfunction, weight gain, hot flushes and mood swings may bea deterrent for some patients, only 2% of males actively refusedthe treatment and the finding that older males who can beexpected to less concerned about some of these side effect were

J. Wang et al. / The Breast 18 (2009) 378–381 381

less likely to use Tamoxifen did not support this assertion. It maybe that these patients had a past history or significant co-morbidities that put them at increased risk of adverse outcomessuch as thromboembolic disease or stroke, which are morecommon among elderly men.

The survival of male patients may be affected by receiving lessvigorous treatment than female patients. It is particularlyimportant that all factors are considered to ensure that malebreast cancer patients also receive appropriate adjuvant thera-pies even after mastectomy. Axillary lymph node involvementshould be a major factor determining the use of adjuvant therapyas reported previously.14 This study found that there were notsignificantly more LNþ tumours in males when compared withthe female groups. Therefore, the lower rate of radiotherapy andother adjuvant therapy use is particularly concerning. Thisfinding on the lower rate of adjuvant therapy use in males isprobably partly linked to the lack of clear guidelines for malebreast treatment and the generally older age of males with breastcancer. The effect of patient preference is also highlighted by therefusal of some adjuvant therapies by a small number of patientsalthough the likelihood of refusal is not more in males than infemales.

Overall, the results of this study indicate that the histopatho-logical characteristics of the male breast cancer were similar orslightly better than comparable females. Mastectomy was used bymost male patients while a high proportion also underwent axillarydissection. Comparing with the females, males seemed to be twicemore likely to receive no surgical treatment. They were also lesslikely to undergo adjuvant therapies, probably as a result ofmastectomy although males were still less likely to receivechemotherapy comparing with females who have receivedmastectomy.

Conflict of interest statement

The authors state there are no conflicts of interest.

Role of the funding source

For the period June 2006–June 2009, the NBCA was funded byNational Breast and Ovarian Cancer Centre with funds madeavailable through the National Breast Cancer Foundation. Repre-sentatives from both organisations have been members of theNBCA Steering Committee; however the funding bodies have hadno input and are not authors on this manuscript.

Acknowledgements

Regarding the submission of the manuscript ‘‘Are male breastcancer patients treated differently from female breast cancerpatients in Australia and New Zealand?’’ the authors andthe National Breast Cancer Audit would like to gratefullyacknowledge:

� The National Breast Cancer Centre, for generously supportingthe National Breast Cancer Audit through funding madeavailable by the National Breast Cancer Foundation for theperiod of June 2006–June 2009.� The National Breast Cancer Audit Steering Committee.� The surgeons who contributed their data.

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