Journal of Breast Cancer ISSN J Breast Cancer 2007; September 10 (3): ORIGINAL ARTICLE 70 세이상유방암환자의임상적특징과치료결과 이정선ㆍ홍수정ㆍ김희정ㆍ손병호ㆍ김성배 1
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1 Journal of Breast Cancer ISSN J Breast Cancer 2007; September 10 (3): ORIGINAL ARTICLE 70 세이상유방암환자의임상적특징과치료결과 이정선ㆍ홍수정ㆍ김희정ㆍ손병호ㆍ김성배 1 ㆍ안진희 1 ㆍ안승도 2 ㆍ안세현 울산대학교의과대학서울아산병원외과학교실, 1 종양내과교실, 2 방사선종양학과교실 The Clinical Characteristics and Outcome of Breast Cancer Patients Older than 70 Years Jung Sun Lee, Soo Jung Hong, Hee Jeong Kim, Byung Ho Son, Sung Bae Kim 1, Jin Hee Ahn 1, Seung Do Ahn 2, Sei Hyun Ahn Departments of Surgery, 1 Oncology, and 2 Radiologic Oncology, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea Purpose: There is no concensus on the type of therapy useful for elderly cancer patients. Since 2000, Korea has become an elderly society. This study aims to assess clinical characteristics of elderly breast cancer women, and to evaluate determinants and effects of treatment choice for breast cancer prognosis among elderly patients. Methods: We reviewed the clinical reports of 123 breast cancer patients aged 70 yr recorded at the Asan Medical Center Breast Cancer Registry between 1992 and Patient and tumor chariteristics, comorbidity, surgical method, adjuvant therapy and cause of death were taken into consideration. Survival analysis was determined according to the treatment method. Results: The median time to diagnosis was 33.6 months. Only 9 patients (5.1%) were diagnosed in the screening program. A modified radical mastectomy was performed for 74 patients (60.1%), Breast conserving surgery was performed for 26 patients (24.7%), and there was no further curative therapy for 12 patients (9.7%). 32 patients (38.1%) had axillary lymph node metastasis. The median follow-up duration was 43.1 months; the overall survival rate was 71.8%, and the disease free survival rate was 65.4%. Breast cancer related mortality was 62.8%. Conclusion: Delayed diagnosis and infrequent screening were frequent among elderly patients. Cancer related morbidity was less than general breast cancer patients. Treatment needs to be adapted to the general health status of the patient and comorbid conditions, but has to offer the best chance of cure, regardless of age. Key Words : Elderly women, Breast cancer, Adjuvant therapy 중심단어 : 고령여성, 유방암, 보조치료 서 서구의통계를보면전체인구의평균수명은꾸준히증가하여, 1980년대에는전체인구의 11.3% 가 65 세이상인반면, 2030년도에는 75 세이상인구가 20% 에이를것으로추정된다.(1) 환자 책임저자 : 안세현 서울시송파구풍납동 388-1, 울산대학교의과대학서울아산병원외과 Tel: , Fax: ahnsh@amc.seoul.kr 접수일 : 2007 년 2 월 16 일게재승인일 : 2007 년 8 월 6 일 * 본연구는 2006 년도한국유방암학회춘계학술대회에서포스터전시되었음. 론 의나이는유방암치료와역학적인면에서중요한역할을한다. 서구사회에서새로진단된유방암환자의 50-60% 가 65 세이상여성이며, 약 40% 의환자가 70 세이상이다. 의학의발달로건강한여성의기대수명은 21 세기들어증가되고있어, 65 세이상의여성은기대수명이 18.8년, 75 세여성은 11.9년, 85 세여성은 6 년이상이다.(2) 고령의여성에서질환과그에따른위험도는나이가들면서증가되어고령화사회로접어드는사회일수록고령인구에서발생하는유방암이중요한공중보건의문제가되고있다.(3) 유엔기준으로총인구중65세이상의노인의비중이 7% 를넘으면 고령화사회, 14% 를넘으면 고령사회, 20% 를넘으면 초고령사회 라한다. 통계청자료에따르면우리나라는 199
2 200 Jung Sun Lee, et al. 2000년 65세이상의인구비중이 7% 를넘어서면서고령화사회에진입했다고한다. 이러한추세라면 2019년고령사회 (14.4%), 2026년초고령사회 (20%) 에진입할것으로예상된다 ( 대한민국통계청고령자통계, 2004). 고령여성에서발생하는유방암환자의수는증가되고있으나, 종양생물학적특징과임상적인양상에대해서는알려진바는적다. 대부분의임상연구에서고령의환자들이포함되지않거나, 치료가능한고령의환자들의보조치료후결과에대한전향적인임상연구들이부족하여환자의치료방침을세우는데어려움이많다. 고령의유방암환자들과보호자들은고령인점과동반된내과적인질환으로인하여수술및마취, 수술후보조치료를기피하는태도를보인다. 수술후보조치료가삶의질에미치는효과에대한다양한의견들과동반된내과질환이치료에미치는영향으로인해고령의유방암환자치료에대한상반되는의견들이나오는것이사실이다.(4, 5) 저자들은고령화되고있는한국사회에서 70 세유방암환자들의임상양상및치료결과를조사하여고령의유방암환자들의치료에도움이되고자하였다. 방법 1. 대상 1992년 1월부터 2002년 12월까지서울아산병원에서유방암진단및수술을받은 3,987명환자중진단당시 70 세이상의환자 123 명을대상으로하였다. 유방암의병기분류는제 5차 AJCC 분류방법을사용하였다. 2. 방법병원의무기록을통하여종양의크기, 전이된액와림프절개수, 절제된림프절개수, 호르몬수용체상태, 병기를확인하고증상후진단까지걸린시간, 유방암정기검진력, 주증상, 수술후보조치료, 동반된내과질환, 사망원인을조사하였다. 추적방법은주로병원전산시스템과의무기록을이용하였다. 대상환자들의평균추적관찰기간은 43.1개월이었다. 본연구자들의경우유방암환자들의자료는수술시유방암등록기록지를이용해미리데이터베이스화하였기때문에비교적정확한자료를이용할수있었고, 필요한경우는의무기록을추가로이용하였다. 전체생존율, 수술및보조치료방법에따른생존율, 예후인자를조사하였다. 호르몬수용체여부에대해면역조직화학검사를사용하여, 핵염색정도에따라각각 0-3 으로나누어점수를매긴뒤그두점수를합하여최종점수를판정하였다. 0점은 Negative, 1-3점은 Weak Positive, 4-5점은 Intermediate Positive, 6-7점은 Strong Positive로정하였고, 호르몬수용체양성은에스트로겐수용체또는프로게스테론수용체가 4점이상인경우로정하였다. HER-2의경우에는면역조직화학검사상 3+ 이상인경우를과발현이있는것으로판정하였다. 3. 통계처리 사용된통계방법은 Window용 SPSS (Version 11.0; SPSS lnc, Chicago, USA) 을이용하여예후에관련된인자들에따른전체생존율은 Keplan-Meier 분석법을이용하여계산하였고, 생존곡선은 log-rank test를사용하여비교하였다. 다변량분석은 Cox multivariate regression model을사용하였다. p 값이 0.05 미만인경우에통계적유의성이있는것으로간주하였고, 0.1 미만인경우에경계역유의수준으로간주하였다. 1. 대상환자의임상적특징 결 대상환자의평균연령은 74.3 (±3.8) 세이었고, 80세이상인환자는 23명 (19%) 이었다. 가족력이있는환자는 5명 (4.5%) 이었으며, 폐경후호르몬치료를받은환자는 2명 (3.2%) 이었다. 유방암이외의악성종양으로치료받은적인있는환자는 3명 ( 대장암 2명, 외음순암 1명 ) 이었다. 검진상이상이발견되어진단받은환자는 9명 (5.1%) 이었으며, 대부분증상이있어발견되었다. 증상발생후진단까지소요된기간은평균 33.6개월이며, 과거유방암검진을받아본경험이있는경우는 20명 (16.5%) 이었다. 평균종양의크기는 3.1 (±2.1) cm이고, 절제된액와림프절의개수는평균 14.7 (±6.7) 개, 전이된림프절개수는평균 1.9 (±4.3) 개였다. 수술을거부한경우는 23명 (18.6%) 이었으며, 유방절제술을받은경우는 74예 (60.1%), 유방보존수술은 26예 (24.7%) 였다. 병기별분류는 0기인환자가 7명 (5.6%), 1기환자가 27 명 (21.9%), 2기환자가 71명 (57.7%), 3기환자가 9명 (7.3%), 4기인환자가 9명 (7.3%) 이었다. 병리적진단은침윤성유관암이 114명 (92.7%) 이었으며상피내암이 7명 (6%), 침유선소엽암이 1 명 (0.9%) 이었다. 액와림프절절제를시행한 84 명중림프절전이 가있는경우는 32 명 (38.1%) 이었다. 호르몬수용체가양성인경 Table 1. Characteristics among women aged 70 yr with breast cancer Mean age (yr) 74.3 (±3.8) Mean tumor size (cm) 3.1 (±2.1) Mean No. of metastatic lymph node 1.9 (±4.3) Mean No. of dissected lymph node 14.7 (±6.7) 과 No. of patients
3 Breast Cancer in the Elderly 201 우는 70명 (63.1%) 이며, 에스트로겐및프로게스테론수용체모두음성인경우는 41명 (40.6%) 이었다. HER-2/neu를검사한 60명의환자중 15 명 (25%) 에서과발현이나타났다 (Table 1, 2). Table 2. Characteristics among women aged 70 yr with breast cancer No. of patients % Operation method MRM BCO None Stage I II III IV Hormone receptor status (N=111) Positive Negative Lymph node metastasis (N=84) Negative Positive HER-2/neu (IHC >2) (N=60) No amplification Amplication Histologic type Ductal Lobular Other MRM=Modified radical mastectomy; BCO=Breast conserving operation; IHC=Immunohistochemistry. 2. 보조치료방법와전체생존율 전체환자중보조치료로항암치료를한경우는 16 명이며, 경구 Table 3. Distribution of adjuvant systemic therapy according to lymph node and hormone receptor status and outcome according to adjuvant therapy No. of patients No. of event Median survival time (months) p- value* HR (-) LN (-) None CTx 6 0 Total 25 8 LN (+) None CTx Total 15 9 HR (-) None CTx HR (+) LN (-) Adjuvant Hormone Therapy LN (+) Adjuvant Hormone Therapy Alone Adjuvnat 5 0 nc Hormone Therapy+ CTx HR=Hormone receptor (Estrogen receptor or Progesteron receptor); CTx=sytemic chemotherapy or Doxifluridine; nc=not countable. *Log-rank test. 1.2 Overall survival Stage III Overall survival 4 N=3 1.0 Stage II N=2 Cumulative survival rate Stage I Stage Cumulative survival rate N=1 1 N= Follow up duration (month) Fig 1. Overall survival according to stage. Log-rank test p< Follow up duration (month) Fig 2. Overall survival according to axillary lymph node metastasis. Log-rank test p=0.05.
4 202 Jung Sun Lee, et al. Cumulative survival rate 용항암제를복용한경우는 5명이었다. 전신항암치료중항암제부작용인심장독성을보인환자는 1명 (6.2%) 이었다. 액와부림프절전이가없고, 호르몬수용체음성인환자 25 명중항암치료를받은경우는 6명이었다. 림프절전이가있고, 호르몬수용체음성인환자 15 명중항암치료를받은환자는 5명이었다. 림프절전이가있고, 호르몬수용체양성인환자중보조항암치료와항호르몬치료를한환자는 5명이었고, 항호르몬치료만받은환자는 19 명이었다. 림프절전이가없고호르몬수용체양성인환자는모두항호르몬치료를받았다. 각각의치료에따른평균생존기간은 Table 3과같다. 방사선치료는종양의크기가 10 cm 이상이거나림프절전이가 5개이상인경우인 6명모두에서시행되었으며, 유방보존수술받은 26 명의환자중방사선치료를시행한경우는 5명 (19.2%) 이었다. 유방보존수술을받은환자중관찰기간동안국소재발이발견된경우는 4명 (19.1%) 이었으며, 모두방사선치료를받지않은환자에서발생하였다. 수술한환자는평균생존기간이 98 개월인반면수술을거부한환자들의평균생존기간 21 개월로, 수술을안받은환자들은예후가나빴다. 3. 예후인자와생존율 Overall survival rate HR positive negative Follow up duration (month) Fig 3. Overall survival according to hormone receptor status. Logrank test p= 예후인자분석에서단변량분석을통하여병기, 림프절전이, 호르몬수용체가통계적으로의미있었으며 (Table 4, Fig 1-3), 다변량분석에서호르몬수용체와액와부림프절전이여부가통계적으로의미가있었다 (p=0.001, p=0.026) (Table 5). Table 4. Univariate analysis of factors affecting overall survival Variables Stage < * I 27 96* II III 9 48 IV 9 21 HR status Positive Negative N stage 0.05 N0 109 N1 95* N2 65 N3 46 Adjuvant chemotherapy yes 16 60* 0.28 no Operation method MRM BCO 사망원인 평균관찰기간 43.1개월로서, 121명의환자중관찰기간중국소재발된환자는 8명, 전신전이된환자는 12 명, 사망한환자는 35 명이었다. 사망원인은유방암으로인한사망이 22 명 (62.8%) 이었다. 유방암의외의원인으로사망한경우는 13 명으로당뇨의합병증으로사망한경우가 1명, 폐합병증으로사망한경우가 3명, 뇌졸중으로사망한경우가 2명, 기존의악성질환으로사망한경우 4명, 약물중독으로사망한경우 1명, 장천공으로인한사망 1명이었다. 고 유방암의발생빈도가증가되어 2006년미국에서 212,920명의유방암환자가발생하였고, 2006년도한해 40-59세전체여성의 4.11% 에서 70세이상여성에서는 7.13% 발생하였다.(6) 1989년 1월부터 2004년 12 월까지본원에서치료받은환자 5,001명의 찰 Median suvival time (months) p-value MRM=Modified radical mastectomy; BCO=Breast conserving operation; HR=Estrogen receptor or/and progesterone receptor. *Mean survival (median is not achieved); Log-rank test. Table 5. Multivariate analysis on factors affecting overall survival Variables RP 95% CI p-value HR Axillary LN status LN=Lymph node metastasis; HR=Estrogen receptor or/and progesterone receptor.
5 Breast Cancer in the Elderly 203 환자중 60-69세환자는 428명 (8.6%), 70세이상인환자는 179 명 (3.6%) 이었다.(7) 한국사회는아직서구사회처럼고령화된인구가많지않고, 폐경전유방암환자의비율이높기는하지만고령화사회로진입하는속도가빠르기때문에고령의여성에서발생하는유방암의적절한치료에대한다방면의논의는필요하다. 고령의유방암환자들에서평균증상이발생한이후진단을받기까지걸리는시간은평균 33.4개월로, 2004년도한국유방암학회에서보고한한국유방암환자의생존자료 (8) 와비교하면, 3 개월이내에진단되는경우가전체환자 5,322명중 64.5% 인점에비하면상당히길게나타났다. 검진을통해진단되는경우도전체환자 5,322명의환자중 17.6% 인것과비교하면고령의유방암환자들이검진을통해발견되는경우는 5.1% 로적었다. 병기별분포도전체유방암환자 5,322명의환자중 0기와 1기환자가 45.2% 이었으나, 본연구에서는 0기와 1기유방암환자가 27.5% 를차지하여, 조기유방암환자의비율이낮음을알수있었다. 고령유방암환자들의선별검사와치료권고안은일정하지않고젊은여성들과다른면이있다.(9) 미국노인학회임상실행위원회 (American Geriatrics Society Clinical Practice Committee) 가제정한노인유방암환자의선별검사는 75 세까지매년또는 2년마다유방촬영술을시행하고, 생존예측기간이 4년이상이라면 2년마다또는 3년마다시행할것을권유한다. 이런선별검사의효과는매년또는 2년마다유방촬영술을시행하는경우 50 세에서 75 세여성에서유방암관련사망률을 25-30% 낮추는것으로알려져있다.(10) 띠라서고령의여성에서도유방촬영술과자가검진의중요성에대한교육은검진의사를통하여지속되어야하겠다.(11) 일반적으로건강한 70 세이상의환자에서는일차유방암의치료원칙이유방절제술과액와림프절곽청술또는유방보존술과액와림프절곽청술, 방사선요법이포함된다. 70 세이상환자의수술로인한사망률은매우낮아 1-2% 정도이며,(12) 수술후합병증은환자의연령이아닌환자의동반된질환이원인되는경우가많았다.(13) 본연구결과고령의유방암환자에서수술로인한합병증및사망률은없었다. 수술치료는 65세이상고령의유방암환자와 50-64세유방암환자에서국소재발률및전체생존율에유사한영향을미치며, 65 세이상환자에서는유방암이아닌다른동반질환으로인한사망률이오히려높았다 (1% vs 2%; p=0.0006).(14) 유방보존수술이후방사선치료시 10 년간국소구역재발률은 65 세이상에서 4% 인점에비해, 65 세미만의여성에서는 13% 발생하여고령의환자들에게효과적으로나타났다.(15) 고령의환자에서방사선치료없이광범위한국소절제시치료효과는 71-97% 에이르지만방사선치료를시행한경우보다낮은국소치료효과를보였다. 따라서고 령이라는이유만으로방사선치료를제한하는것은적절하지않다. 수술방법을선택하는경우 70 세이상인환자들은유방보존수술보다유방절제수술을많이받는편인데, 본연구에서도유방절제술을시행하는경우가많았다. 그러나수술방법이예후과관련된인자가아니고고령의환자들도환자자신의신체이미지에영향을미치므로수술방법을선택하는경우유방보존수술을선택할수있도록제시할필요가있다. 대규모임상연구들은고령의환자들을포함시키지않으며,(16) 치료방법도고령환자의유방암이젊은여성의유방암보다느리게자란다는잘못된개념이나치료자의선호도에의해치료되는경향이있다. 다양한치료방침과치료결과에대한충분한평가도고령의환자들에게이루어지지않는경향이있다.(17-19) Gajdos 등 (20) 은고령의유방암환자들의예후가좋은이유는고령환자의유방암은 S-phase fraction이낮고, p53이정상이며, EGFR 발현이적은양호한종양생물학적특징을가진다고하였다.(21) 하지만 Pappo 등 (22) 은 70 세이상환자들과 70 세미만인환자들사이에이런변수들의차이는없으며, 세포증식과관련된표지자중 thymidine-3h labeling index가낮고, diploid type의빈도가높고, 조직학적분화도가낮다고하였고, 정상 p53 빈도가높고, EGF-1, Her-2/neu 발현빈도가적다고하였다. Honma 등은 85세이상의폐경후유방암환자에서는프로게스테론수용체의양성이다소적고, 안드로겐수용체의양성이높으며, 폐경후여성의체내여성호르몬의급감하는것과관련되어, 안드로젠과안드로젠수용체가상대적으로고령의여성에서발생하는유방암의병리기전에영향을미친다고보고하였다.(23) 이는폐경후유방암환자의자연경과와원인를설명하기위해점차적으로연구되어져야하는영역이기도하다. EBCTCG는 1998년 5년추적관찰의메타분석에서도 70 세이상유방암환자에서보조항암요법과항호르몬치료는조기, 호르몬수용체양성인환자에서재발률감소와전체생존율향상에도움이된다고하였다.(24) 호르몬수용체양성인환자에서타목시펜과항암요법의병합요법이각각의단독사용보다재발률과생존율향상에이득을보였으며, 70 세이상의환자수가 600 명으로항암요법의이득을평각하기에충분한수는아니지만폐경기환자에서도 50-69세환자와 70세이상환자에서항암요법의상대적이득이유사하였다.(24) 유방암이외의다른원인에의해사망하기때문에전체생존율이낮아지는것이므로, 전신상태가양호한고령의환자에게는적절한항암요법을시행하는것이고려된다. 본연구에서도보조항암요법에따른치료효과를평가할만큼충분한환자수가아니었으나 70 세이상의호르몬수용체음성인환자들중림프절전이가있는환자에서는보조항암치료받은환자들의평균생존기간이경계적수준으로증가되었으나, 호
6 204 Jung Sun Lee, et al. 르몬수용체양성인경우는본연구에서는항암요법의이득을알수는없었다. 유방암환자들의동반된기저질환은고령유방암환자의치료선택시중요한인자가되고있다. 나이가증가되면서환자의동반질환의수는증가되어, 65 세이상의환자들은 65 세미만의환자에비해유방암이아닌다른원인으로사망하는경우가많아진다. 더구나기능적인장애가유발되고진행성인당뇨, 만성페질환, 심혈관계질환들은주요사인으로나이가증가될수록증가한다. Satariano 등은동반질환이없는경우에비해동반된주요질환이 1개인환자는상대위험도가 2.5, 2개이상인경우는상대위험도 3.4 라고하였다. 이런동반된질환들은보조치료로인한합병증과사망률에도영향을미친다고한다.(25) 본연구에서는개인의동반질환에따른사망률과보조치료에미치는영향을알수없었으나향후동반된질환이생존율과보조치료과정에미치는영향에대해연구할필요성을알수있었다. 결론고령의유방암환자들은대부분증상이있어발견되는경우가많았고, 증상이발생되어진단및치료받기까지의기간이길었으며, 조기유방암환자의비율이낮았다. 수술과마취로인한사망률은없었고, 노환보다는유방암에의한사망이많았으나, 다른연령에비하여유방암이외의원인으로사망하는경우가많았다. 고령의유방암환자들에게는환자개개인마다동반된질환들과유방암수술재발위험도와보조치료로인한부작용을고려하여환자와보호자와상의하여적절한국소및전신치료를받도록할필요가있음을알수있었다. 참고문헌 1. Holmes CE, Muss HB. Diagnosis and treatment of breast cancer in the elderly. CA Cancer J Clin 2003;53: Crivellari D, Bonetti M, Castiglione-Gertsch, Gelber RD, Rudenstam CM, Thurlimann B, et al. Burdens and benefits of adjuvant Cyclophosphamide, Methotrexate, and Fluorouracil and Tamoxifen for elderly patients with breast cancer: the international breast cancer study group trial VII. J Clin Oncol 2000;18: Parkin DM, Muir CS. Cancer Incidence in Five continents. Comparability and quality of data. IARC Sci Publ 1992;120: De Haes H, Curran D, Aaronson NK, Fentiman IS. Quality of life in breast cancer patients aged over 70 years, participating in the EORTC randomized clinical trial. Eur J Cancer 2003;39: Newschaffer CJ, Penberthy L, Desch CE, Retchin SM, Whittemore M. The effect of age and comorbidity in the treatment of elderly women with nonmetastatic breast cancer. Arch Intern Med 1996;156: Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer charateristics, CA Cancer J Clin 2006;56: Son BH, Kwack BS, Kim JK, Kim HJ, Hong SJ, Lee JS, et al. Changing patterns in the clinical charateristics of Korean Patients with breast cancer during the last 15 years. Arch Surg 2006;141: Gong G, Kim MJ, Shim YH, Kang GH, Ahn SH, Ro JY, et al. Nationwide Korean breast cancer data of 2004 using breast cancer registration program. Korean Breast Cacner Soc 2006;9: Goldhirsch A, Glick JH, Gelber RD, Senn HJ. Meeting highlights: International Consensus Panel on the treatment of primary breast cancer. J Natl Cancer Inst 1998;90: Kerlikowske K, Grady D, Rubin SM, Sandrock C, Ernster VL. Efficacy of screening mammography: a meta analysis. JAMA 1995;273: Thomas LR, Fox SA, Leake BG, Roetzheim RG. The effects of health beliefs on screening mammography utilization among a diverse sample of older women. Women Health 1996;24: Turnbull AD, Gundy E, Howland WS, Beattle EJ Jr. Surgical mortality among the elderly. An analysis of 4050 operations ( ). Clin Bull 1978;8: Yancik R, Ries LG, Yates JW. Breast cancer in aging women: a population-based study of contrasts in stage, surgery, and survival. Cancer 1989;63: Solin LJ, Schultz DJ, Fowble BL. Ten-year results of the treatment of early-stage breast carcinoma in elderly women using breast conserving surgery and definitive breast irradiation. Int J Radiat Oncol Biol Phys 1995;33: Merchant TE, McCormick B, Yahalom J, Borgen P. The influence of old age on breast cancer treatment decisions and outcome. Int J Radiat Oncol Biol Phys 1996;34: Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underpresentation of patients 65years of age or older in cancer-treatment trials. N Engl J Med 1999;341: Silliman RA, Troyan SL Guadagnoli E, Kaplan SH, Greenfield S. The impact of age, marital status, and physician-patients interactions on the care of older women with breast carcinoma. Cancer 1997;80: Mandelblatt JS, Handley J, Kerner JF, Schulman KA, Gold K, Dun-
7 Breast Cancer in the Elderly 205 more-griffith J, et al. Patterns of breast carcinoma treatment in older women: patients preference and clinical and physical influences. Cancer 2000;89: Busch E, Kemeny M, Fremgen A, Osteen RT, Winchester DP, Clive RE. Patterns of breast cancer care in the elderly. Cancer 1996;78: Gajdos C, Tartter PI, Bleiweiss IJ, Lopchinsky RA, Bernstein JL. The consequence of undertreating breast cancer in the elderly. J Am Coll Surg 2001;192: Diab SG, Elledge RM, Clark GM. Tumor charateristics and clinical outcome of elderly women with breast cancer. J Natl Cancer Inst 2000; 92: Pappo I, Karni T, Sandbank J, Dinur I, Sella A, Stahl-Kent V, et al. Breast cancer in the elderly: histological, hormonal and surgical charateristics. Breast 2007;16: Honma N, Sakamoto G, Akiyama F, Esaki Y, Sawabe M, Arai T, et al. Breast carcinoma in women over the age of 85: distinct histological pattern and androgen, estrogen,and progesterone receptor status. Histopathology 2003;42: Early Breast Cancer Trialists Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 1998;352: Satariano WA. Aging, comorbidity, and breast cancer survival: an epidermiologic view. Adv Exp Med Biol 1993;330:1-11.
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