A comparison outcome of male breast cancer with female breast cancer

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  • A Comparison Outcome of Male Breast Cancer with Female Breast Cancer

    Peter C. Willsher, FRACS, lain H. Leach, DM, Ian 0. Ellis, MRCPath, Jim B. Bourke, FRCS, Roger W. Blarney, FRCS, John F.R. Robertson, FRCS, Nottingham, United Kingdom

    BACKGROUND: It is unclear whether breast cancer has a similar prognosis in males and females.

    METHODS: A 20-year retrospective study of all male breast cancer patients in our region was un- dertaken. We compared this series with a group of females matched for the major prognostic fac- tors and an unmatched series of female patients treated over the same period.

    RESULTS: Forty-one patients with invasive cancer and 2 with ductal carcinoma in situ were identi- fied. One invasive cancer was treated with radio- therapy, 40 had surgery. Local recurrence oc- curred in 23% and axillary recurrence in 40% of cases. Male and female patients (n = 123) matched for the major prognostic factors showed a similar outcome for disease-free interval (P = 0.90) and survival (P = 0.27). However, both the above groups had a significantly worse outcome than the unmatched series of female patients with breast cancer.

    CONCLUSIONS: When prognostic factors are al- lowed for, male and female breast cancer pa- tients have a similar outcome. This suggests that such features should be taken into account when determining management for males with breast cancer just as they are in females. Am J Surg. 1997;173:135-139. 0 1997 by Excerpta Medica, Inc.

    I t would appear that much of the management of male breast cancer is based on clinical experience gained from treating females with breast cancer.- However, reports in the literature are conflicting as to whether male breast cancer has a prognosis and clinical course similar to female breast cancer. We have undertaken a retrospective study of a series of male patients with breast cancer and compared the outcome with a group of matched female breast cancer patients.

    METHODS Patients

    Male patients who presented with breast cancer to any of the general surgeons at the three major hospitals in Not-

    From the Professorial Unit of Surgery and Department of His- topathology, City Hospital and Department of Surgery, University Hospital, Nottingham, United Kingdom.

    Requests for reprints should be addressed to Peter C. Willsher, FRACS, Professorial Unit of Surgery, City Hospital, Hucknall Road, Nottingham NG5 1 PB, United Kingdom.

    Manuscript submitted October 4, 1995 and accepted in revised form March 25, 1996.

    tingham during the 20-year period prior to June 1994 were identified in the following manner. All consultant surgeons were written to request permission to gather information on their patients, and were asked for details of male breast can- cer patients they could recall treating. All consultants re- plied, providing an initial list of patients. Following this, the Trent Regional Cancer Registry provided a list of all male breast cancer patients listed for each general surgeon in Nottingham over the previous 20 years. Finally, a review of the records of the hospital pathology departments was undertaken. A total of 43 male patients with a histological diagnosis of breast cancer were identified. The case notes of all patients were reviewed, and the clinical data obtained.

    Matching of Male and Female Patients For each of the 41 male patients with invasive cancer, 3

    female breast cancer patients (n = 123) were matched to allow comparison of disease-free interval and survival. The female patients were obtained from a computerized database of over 3,000 patients treated in our unit over a 20-year period. Patients were matched for age, pathological size and grade of primary tumor, and pathological lymph node status (Table I). The groups were well matched for these factors apart from the lymph node status, since this was unknown in a large proportion of male patients. The matched female patients were diagnosed not more than 12 months from the date of diagnosis of each correspondmg male patient.

    Statistical Analyses All analyses were performed with the SPSS-X data anal-

    ysis program (SPSS UK Ltd.). Fishers exact test (two tailed) was used to assess for differences in proportions. Dis- ease-free interval and survival curves were compared with the Lee-Desu statistic using Gehans modification of the generalized Wilcoxon test. Degrees of freedom was n - 1 for all analyses.

    RESULTS Clinical Features

    The 43 patients in the study comprised 2 with ductal car- cinoma in situ and 41 with invasive breast cancer. Of the 41 invasive cancers, 24 were in the left breast and 17 in the right. Patients had experienced symptoms for an average of 6 months prior to presentation (range 1 week to 3 years). For the patients with invasive cancer, 88% (36 of 41) com- plained of a lump at the time of presentation. Three re- ported a serosanguineous nipple discharge alone, 1 had pain only, and 1 patient with Pagets disease complained of nip- ple deformity only. On examination 950/o (39 of 41) of pa- tients had a palpable lump, the retnaining 2 had a nipple discharge only detected. Five patients had palpable axillary

    % 1997 by Excerpta Medica, Inc. 0002-961 O/97/$1 7.00 185 All rights reserved. PII SOOO2-9610(97)00009-3


    Characteristics of Matched Male and Female Patients

    Male Patients (n = 41)

    Female Patients In = 123)

    Mean age (range) Mean pathological

    size (range) Pathological grade

    II Ill

    Axillaty node status

    Positive Negative Unknown

    63 years (32-96) 61 years (29-85)

    24 mm (l-110) 25 mm (2-80)

    1 (2%) 11 (27%) 29 (70%)

    10 (24%) 8 (20%)

    23 (56%)

    3 (2%)

    32 (26%)

    88 (71%)

    34 (28%)

    76 (62%)

    13 (10%)


    Local Recurrence in Operable Patients (n = 40)

    Recurrence Recurrence Rate After Rate Without

    Type of Operation Radiotherapy Radiotherapy

    Local excision (n = 4)

    Simple mastectomy (n = 18)

    Simple mastectomy and excision of axillaty nodes (n = 18)

    Total (n = 40)

    0% (O/2) 0% (O/2)

    33% (l/3) 20% (3/15)

    0% (Oh) 38% (5/13) 10% (l/10) 27% (8/30)

    TABLE Ill

    lpsilateral Axillaty Node Recurrence in Operable Patients (n = 40)

    Recurrence Recurrence Rate After Rate Without

    Radiotherapy Radiotherapy

    Pathological node positive (n = 10) 0% (O/2) 75% (6/8)

    Pathological node negative (n = 8) 0% (O/2) 50% (3/6)

    Nodes not sampled (n = 22) 33% (2/6) 38% (5/16)

    Total (n = 40) 20% (2/l 0) 47% (14/30)

    nodes, and no patient had distant metastases detected at the time of presentation.

    Initial Treatment and Clinical Outcome Of the 2 patients with ductal carcinoma in situ, 1 had a

    mastectomy and the other a local excision of the palpable lump. Of the 41 patients with invasive cancer, 1 had a locally advanced tumor (11 cm diameter) and was initially treated with radiotherapy. The remaining 40 patients un- derwent surgery; 4 had lumpectomy alone, 18 simple mas- tectomy, and 18 mastectomy with excision of axillary nodes. The mean number of nodes removed was 2.8 (range 1 to 7). Of the 40 patients with operable tumors, 11 re-


    0.3 1 1 0 12 24 36 46 60 72

    Months from Diagnosis

    Figure 1. Comparison of disease-free interval for male and matched female patients with breast cancer showing no signifi- cant difference (Lee Desu statistic = 0.02, P = 0.90). Compared with an unmatched female series, both the male patients (statistic = 4.3, P = 0.04) and matched female patients (statistic = 10.4, P = 0.001) have a worse outcome.

    ceived adjuvant therapy (7 local flap and ipsilateral axillary radiotherapy, 3 tamoxifen and radiotherapy, and 1 tamox- ifen only). Adjuvant tamoxifen was given to only 3 of the 10 patients with pathological axillary node involvement. No patient was given adjuvant systemic chemotherapy.

    Neither patient with ductal carcinoma in situ had recurrence of their disease after 1 and 5 years of follow-up. For the 40 patients with operable invasive cancer, local recurrence after surgery occurred in 23%) (9 of 40) at a mean of 15 months (range 6 to 35). Table II shows the local recurrence rate for each type of operation. Local recurrence was more common for histological grade 3 cancers (grade 3, 8 of 29; grade 1 or 2, 1 of II), but this difference wds not si@ficant (P = 0.40). Tumor size larger than 2 cm in diameter (>2 cm 6 of 28,


    Figure 2. Survival curves for male and matched female patients with breast cancer showing no significant difference (Lee Desu statistic = 1.24, P = 0.27). Compared with an unmatched female series, both the male patients (statistic = 8.6, P = 0.0003) and matched female patients (statistic = 7.7, P = 0.006) have a worse outcome.

    the outcome of the entire female series (n = 3,085, median follow-up 40 months) treated during the same period and in the same region as the male series is shown in Figures 1 and 2. This shows that both the male and matched female groups have a worse outcome than the female series as a whole.

    COMMENTS Male breast cancer represents less than 1% of all breast

    cancer, and it is therefore not surprising that this series is retrospective in nature (in common with the previously re- ported series of male breast cancer).4*5 In contrast to fe- male patients with breast cancer, there are no reports where male breast cancer patients have been observed prospec- tively in a randomized trial, and it is unlikely that any such trials will be performed.a6 If any advances in the manage- ment of breast cancer identified in females are to be applied to males with breast cancer, it is important that similarities or differences in clinical outcome between male and female breast cancer are identified.

    Clinical Features and Initial Management The mean age of presentation for males with breast cancer

    is approximately 10 years older than for females., The ma- jority of male patients with breast cancer present with pal- pable lump, as would be expected in view of the small size of the male breast. In this series only 2 patients did not have a clinically detectable breast mass, and these patients hoth had a serosanguineous nipple discharge as their only clinical feature. Other series have reported nipple discharge as a presenting symptom of breast. cancer in men and suggest that it should always be investigated by biopsy.,

    With respect to the management of male breast cancer, review of the literature reveals a gradual shift away from radical mastectomy, which appears to parallel a recognition in female breast cancer that more radical local surgery does not influence survival. There has heen no clinical trial in male breast cancer to prove this, hut retrospective reports show no survival advantage for radical mastectomy.24,h In our series, no patient had a radical mastectomy, and the majority were treated with simple mastectomy, with or

    1 Surviving Fraction

    0.9 /~ 'I1 I ,


    1 o.401---;2---1--- 36-. I

    24 &5 72 Months From Diagnosis

    without node excision. It is of interest that the 4 patients who had lumpectomy (2 with r&c~therapy) have not de- veloped local recurrence (Table II). While breast conser- vation surgery with radiotherapy has become standard ther- apy for female breast cancer, at present no conclusive data regarding this approach in male breast cancer is available.

    The 23% local recurrence rate in our series falls in the upper range of that reported in female breast cancer. It should be noteJ that 73% of tumors were histological grade 3 and that, as in female breast cancer, this series found that patients with higher grade tumors were more likely to de- velop local recurrence. Postoperative radiotherapy did im- prove local control in our series (Table II), and this has been reported by others.4 In view of the known benefits of radiotherapy in female breast cancer, ir would seem prudent to provide postoperative radiotherapy- for all T3 tumors and for T1/2 tumors with a high risk of local recurrence. Tumor grade, axillary node status, and lymph-vascular invasion are predictive of local recurrence in female breast cancer. While these factors are not statistically significant in this small series, this finding would suggest that male patients with such risk factor should he considered for local adjuvant radiotherapy.

    The regional axillary node recurrence rate of 40% (Table III) reflects the conservative manqement of the axilla in this series of patients. Almost half of the patients did not have any initial treatment to the axilla wtth either surgery or radiotherapy. In those who did have axillary surgery, this was largely confined to node sampling. The 10 patients with pathologically involved nodes did not have a full axillary clearance, and only 2 received adjuvant radiotherapy. It should be remembered that some patients in this series were treated up to 20 years ago, and it was notable that earlier patients had excision of palpable axillary nodes only. Latter patients tended to have a four-node axillary sample taken, followed by radiotherapy if node positive. Overall, radio- therapy resulted in a reduction of the regional recurrence rate from 47% to 20% (Table III). This difference was not statistically significant, which may he related to the small size of this series. However, this outcome suggests that the axilla in male breast cancer should he managed as in female breast cancer.

    The role of systemic adjuvant therapy in male breast can- cer is less well established than in female breast cancer. This is confirmed in our series where only 6 patients re- ceived adjuvant tamoxifen. This meant that 7 of the 10 patients known to be axillary node positive did not receive any adjuvant systemic therapy. The infrequency of male breast cancer means that no prospective trial of systemic adjuvant therapy has been performed, so that the benefits have not been proven. Bagley et al and Pate1 et al have compared a total of 35 patients given adjutant chemother- apy for male breast cancer, with retrospective controls to show an improved outcome. Riberio et al obtained a 61% 5-year survival in 35 patients given adjuvant tamoxifen for operable breast cancer, compared w~rh 44% survival in his- torical controls. The authors of these reports admit that their series are small and that the USC of retrospective con- trols does place limitations on their conclusion. However, these reports suggest that a survival henefit similar to female breast cancer could be obtained hy the use of systemic ad- juvant therapy in male breast cancer. Several authors now



    recommend the use of adjuvant treatment in node positive patients.,, Since the benefits are unproved, the role of this therapy in node negative patients is not clear. The majority of male breast cancers are estrogen-receptor posi- tive, and the reported side effects of tamoxifen are few in males. It has been recommended that tamoxifen be the ad- juvant therapy of cho...


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