Improved Prognosis of Women Aged 75 and Older with Mammography-detected Breast Cancer 1

Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. Original Research n Breast Imaging Judith A. Malmgren, PhD Jay Parikh, MD Mary K. Atwood, CTR Henry G. Kaplan, MD Improved Prognosis of Women Aged 75 and Older with Mammography-detected Breast Cancer 1 Purpose: To evaluate the characteristics and outcomes of women aged 75 years and older with mammography-detected breast cancer, an age group not represented in mammography screening effectiveness studies. 1 From HealthStat Consulting, 12025 9th Ave NW, Seattle, WA 98177 (J.A.M.); School of Public Health, Department of Epidemiology, University of Washington, Seattle, Wash (J.A.M.); and Swedish Cancer Institute at Swedish Medical Center, Seattle, Wash (J.P., M.K.A., H.G.K.). Received February 7, 2014; revision requested March 7; revision received May 4; accepted May 14; final version accepted June 2. Supported by the Kaplan Cancer Research Fund. Address correspondence to J.A.M. (e-mail: jmalmgren@ seanet.com). q RSNA, 2014 Materials and Methods: Results: Conclusion: We conducted a HIPAA-compliant, prospective cohort study with waiver of informed consent in patients with primary breast cancer, aged 75 years and older, with stage 0 IV disease from 1990 to 2011, identified and tracked with our registry database (n = 1162). Details including stage, treatment, outcomes, and method of detection (by patient, physician, or mammography) were noted from the chart at the time of diagnosis. Kaplan-Meier estimation was used to compare invasive disease specific survival rates. Among patients with breast cancer aged 75 years and older, mammography detection of cancers increased over time, from 49% to 70% (P,.001). Mammography-detected cases were more often stage I (62%), whereas patient- and physician-detected cases were more likely stage II and III (59%). Over time, from 1990 to 2011, the incidence of stage II cancers decreased by 8%, the incidence of stage III cancers decreased by 8%, and the incidence of stage 0 cancers increased by 15% (P,.001). Patients with mammography-detected invasive breast cancer were more often treated with lumpectomy and radiation and underwent fewer mastectomies and less chemotherapy than patients with cancer detected by patients and physicians (P,.001). Mammography detection was associated with significantly better 5-year disease-specific survival for invasive breast cancer (97% vs 87% for patient- and physician-detected cancer [P,.001], respectively). Mammography-detected breast cancer in women 75 years and older was diagnosed at an earlier stage, required less treatment, and had better disease-specific survival than patient- or physician-detected breast cancer. These findings indicate that the same benefits of mammography detection observed in younger women extend to older women. q RSNA, 2014 Online supplemental material is available for this article. 686 radiology.rsna.org n Radiology: Volume 273: Number 3 December 2014

Women aged 75 years and older represent 21% of cases of breast cancer incidence in the United States and 37% of breast cancer deaths (1). Currently, the U.S. Preventive Services Task Force (2) reports insufficient evidence to assess the benefits and harms of screening mammography for women aged 75 years and older. Advances in Knowledge Mammography-detected breast cancer in patients 75 years and older is diagnosed at an earlier stage than patient- or physiciandetected breast cancer (stage I, 62% [459 of 744 patients] vs 33% [139 of 418 patients], respectively) and is diagnosed less often at a later stage (stage II IV, 20% [146 of 744 patients] vs 64% [267 of 418 patients], respectively). Mammography-detected invasive breast cancer is most often treated with breast-conserving surgery, as compared with patient- and physician-detected breast cancer (87% [524 of 603 patients] vs 56% [217 of 385 patients], respectively), and is treated less often with mastectomy (13% [79 of 603 patients] vs 42% [160 of 385 patients], respectively) and chemotherapy (6% [36 of 603 patients] vs 17% [64 of 385 patients], respectively). Mammography-detected invasive breast cancer cases had a better 5-year disease-specific survival rate than patient- or physiciandetected breast cancer cases (97% vs 87%, respectively). The same benefits of early stage at diagnosis from mammography detection that were observed in younger women less treatment and better survival extend to women aged 75 84 years and may extend to women 85 years and older, depending on life expectancy. In younger women (aged 50 74 years), randomized clinical trials provide evidence of mammography screening effectiveness to detect breast cancer at an earlier stage, with a reduced need for extensive treatment and reduced breast cancer specific mortality (3 5). At the age of 75 years, women in the United States have a mean life expectancy of 13 years; at age 80, life expectancy is 9 years; and at age 85, life expectancy is 7 years (6). Women 70 years and older have the highest 10-year breast cancer risk (one in 15) (7,8). Chemotherapy treatment of older patients with advanced disease is problematic, but the development of more effective radiation therapy, surgical techniques, and hormonal therapy has improved breast cancer treatment for the elderly (9 13). These treatments, however, require disease diagnosis at an early stage to be useful. Screening mammography has a higher sensitivity and specificity in older women than in younger women, and bieial screening mammography among 66- to 89-year-olds has an equivalent capacity in the detection of breast cancer, in terms of age and comorbidity (14,15). However, debate on direct evidence, value, cost, and effectiveness of mammography screening in this oldest age group continues (16,17). The debate includes the value of screening a population with a limited life expectancy, even though life span is expanding Implications for Patient Care When discussing mammography screening with a patient 75 years and older, the potential benefits of less invasive treatment and better survival if breast cancer is discovered with mammography instead of by the patient or her doctor should be added to the conversation. Mammography detection of breast cancer in women aged 75 years and older is associated with a reduction in advancedstage cancer, which has few acceptable systemic treatment options in the elderly. and the aging process is heterogeneous (18,19). The American Cancer Society recommends that women continue participation in mammography screening, regardless of age, as long as they have no serious chronic conditions or shortened life expectancy (20). Our aim was to use our communitybased institutional cohort breast cancer database registry to evaluate characteristics and outcomes of women aged 75 and older with mammography-detected breast cancer, an age group not represented in mammography screening effectiveness studies. Materials and Methods This study was institutional review board approved and compliant with the Health Insurance Portability and Accountability Act. A waiver of informed consent was granted. Data were collected prospectively for all women with primary breast cancer biopsy confirmed to be stage 0 IV from 1990 to 2011, identified and tracked with our dedicated breast cancer registry database (n = 1162). The registry is for all patients with breast cancer seen at our institution with detailed information on method of diagnosis, patient characteristics, stage at diagnosis, and follow-up for disease and mortality outcomes. Clinical presentation characteristics, Published online before print 10.1148/radiol.14140209 Content code: Radiology 2014; 273:686 694 Abbreviations: CI = confidence interval DCIS = ductal carcinoma in situ MamD = mammography detected PhysD = physician detected PtD = patient detected Author contributions: Guarantors of integrity of entire study, J.A.M., H.G.K.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, J.A.M., J.P., H.G.K.; clinical studies, H.G.K.; statistical analysis, J.A.M.; and manuscript editing, all authors Conflicts of interest are listed at the end of this article. Radiology: Volume 273: Number 3 December 2014 n radiology.rsna.org 687

including age, race, stage (according to the American Joint Committee on Cancer staging system, 7th edition) (21), and method of detection (by patient, physician, or mammography) were noted from the chart at the time of diagnosis. A report on part of this patient population (n = 956) has been published previously (12). Registry follow-up is updated on an aual basis by a certified cancer registrar with information on recurrence, subsequent treatment, and vital status, current through 2012. Vital and disease status information was obtained from chart review if the patient was still being seen at our institution or through physician-directed follow-up letter if follow-up care was provided elsewhere. Patients not under the care of a managing physician were contacted by mail by using an institutional review board approved letter from their diagnosing physician, requesting aual follow-up information. If no response was received, the cancer registry at the institution and the Seattle Puget Sound Cancer Surveillance System registry data were reviewed for the patient s vital and disease status (22). By using this method, we had complete ascertainment of vital status for all patients, with 2.6% of patients missing cancer status at follow-up (n = 30). Initial breast cancer detection method information was obtained by a certified cancer registrar who reviewed patient medical records. The methods used to define detection method have been reported previously (23). The three detection methods were mammography detected (MamD), physician detected (PhysD), and patient detected (PtD). A MamD breast cancer refers to disease discovered with routine mammography in the absence of complaints or known physical findings or with repeat mammography to verify a previous equivocal mammographic finding. PtD was assigned if the patient presented with personally detected breast symptoms, such as a palpable lump, pain, swelling, nipple discharge, or bleeding, which prompted examination by a physician. Patients with self-detected tumors may have subsequently undergone mammography or ultrasonography but would still be categorized as having a PtD breast cancer. PhysD was defined as initiation of work-up for breast cancer after physical findings discovered by the physician at a routine visit or a visit for other problems. The detection method designation was only made when it was certain from the record. If the detection method was ambiguous or incomplete, the tumor detection method was marked as unknown, and these patients were excluded from the analysis (n = 117). IBM SPSS Statistics software version 20 (IBM, Armonk, NY) was used for all statistical analysis. The two main comparison groups were MamD breast cancer and manually detected breast cancer (in which the PtD and PhysD breast cancers were combined into one group). PtD and PhysD breast cancers were combined into a single group for the analysis, as the two groups were found to not differ according to any demographic or diagnostic criteria (age, race, stage, hormone receptor status, or recurrence) (Table E1 [online]), and they are both detected manually. Pearson x 2 tests were used for categorical variable statistical comparisons, and the two-sample t test was used for mean comparisons. All P values were two tailed. Forward stepwise logistic regression was used for multivariate modeling to compare MamD breast cancers with PtD and PhysD cancers as the outcome of interest. The Hosmer-Lemeshow test of goodness of fit was used to evaluate how well the model fit the data. The cohort for the survival and Cox proportional hazards regression analysis was restricted to stage I III invasive breast cancer and truncated at diagnosis year 2010 to allow for a minimum 2 years of follow-up for recurrence and mortality (n = 946) (Fig 1). Analysis was conducted by using died of any cause as the outcome for overall survival, breast cancer death for disease-specific survival, and recurrence of breast cancer (local, regional, or distant) for the relapse-free survival. Cox proportional hazards regression modeling was performed for hazard of invasive Figure 1 Figure 1: Flow diagram shows the patient cohort selection process. breast cancer disease-specific death to evaluate the effect of detection method by age. Stage 0 breast cancer (ductal carcinoma in situ [DCIS]) was excluded from the survival and Cox proportional hazards regression analysis to address the potential effect of leadtime bias. All variables in the model fit the proportionality assumption with parallel survival curves when plotted by using the log minus log function. There was no evidence of a violation of the proportional hazards assumption (P,.001). Results Eleven percent of our breast cancer registry cohort (n = 10 935; age range, 20 94 years) were aged 75 years and older (n = 1162) (Table 1). The patients aged 75 years and older were predominately white, with 10% reported as nonwhite race. Over the 21 years of the registry history from 1990 to 2011, 64% (744 of 1162) of the 75 and older breast cancer patients were diagnosed by mammography, and 36% (418 of 1162) were diagnosed by either the patient or the patient s physician. Over time, we observed a 21% increase in MamD breast cancer among patients 75 years 688 radiology.rsna.org n Radiology: Volume 273: Number 3 December 2014

Table 1 Patient and Tumor Characteristics according to Detection Method in Women Aged 75 Years and Older with Stage 0 IV Breast Cancer (n = 1162) Variable Figure 2 No. of Patients with PtD or PhysD Cancer (n = 418) No. of Patients with MamD Cancer (n = 744) Figure 2: Bar graph shows the change in detection method over time (1990 2011) for breast cancer cases in patients aged 75 years and older (n = 1162). Pt/PhysD = detection by patient or physician. P Value Age 75 79 years 207 (50) 411 (55).032 80 84 years 142 (34) 248 (33) 85+ years 69 (16) 85 (11) Mean age (y)* 80.5 (75 94) 79.5 (75 93),.001 Race White 375 (90) 683 (92).539 Asian 25 (6) 39 (5) Black 13 (3) 13 (2) Other 5 (1) 9 (1) Diagnosis year 1990 1994 61 (15) 59 (8),.001 1995 1999 97 (23) 128 (17) 2000 2004 110 (26) 229 (31) 2005 2009 114 (27) 245 (33) 2010 2011 36 (9) 83 (11) TNM stage 0 12 (3) 139 (19),.001 I 139 (33) 459 (62) II 153 (37) 121 (16) III 93 (22) 23 (3) IV 21 (5) 2 (0.3) Mean tumor size (cm) 3.02 1.53,.001 Lymph nodes positive for cancer 157 (38) 92 (12),.001 Estrogen receptor status Estrogen receptor positive 341 (84) [341/408] 612 (93) [612/659],.001 Estrogen receptor negative 67 (16) 47 (6) Note. Numbers in parentheses are percentages, unless indicated otherwise. Numbers in brackets are the data used to calculate the percentages. * Data are mean ages. Numbers in parentheses are age ranges. and older, from 49% in 1990 1994 (59 of 120 patients) to 70% in 2010 2011 (83 of 119 patients) (Table 1, Fig 2). Excluding carcinoma in situ and looking only at stage I IV invasive breast cancer, we observed a 17% increase in MamD breast cancer, from 47% (55 of 116 patients) to 64% (63 of 98 patients) in the same time period (P =.003) (Table 2). Patients with MamD breast cancer versus those with PtD or PhysD cancer differed by age, diagnosis year, stage, tumor size, and estrogen receptor status (Table 1). Patients with MamD cancer were younger (55% were aged 75 79 years [411 of 744 patients]); more likely to have received a diagnosis between 2000 and 2011; more likely to have stage 0 or I cancer; less likely to have stage II, III, or IV cancer; more likely to have estrogen receptor positive status; and more likely to have small tumors (mean diameter, 1.53 cm). As the method of detection changed, we observed a stage shift over time, with an 8% decrease in stage II breast cancer from 28% (33 of 120 patients) in 1990 1994 to 20% (24 of 119 patients) in 2010 2011, an 8% decrease in stage III cancer from 18% (21 of 120 patients) in 1990 1994 to 10% (12 of 119 patients) in 2010 2011, and an increase in stage 0 cancer (DCIS) from 3% (four of 120 patients) in 1990 1994 to 18% (21 of 119 patients) in 2010 2011 (P =.007) (Table 3, Fig 3). Rates of stage I and IV breast cancer diagnosis did not change substantially over the same time period. In forward stepwise logistic regression, order of entry into the model with mammography detection as the outcome was: 1. Stage 0 or I cancer 2. Estrogen receptor positive status 3. Diagnosis assigned in 2000 2011 4. Age of 75 84 years (Table 4). MamD cancer was significantly less frequent among the patients 85 years and older 55% among 85 94-year-olds (85 of 154 patients) with no significant difference in stage at diagnosis or cause of death when compared with the 75 84-year-olds (Table 5). The patients Radiology: Volume 273: Number 3 December 2014 n radiology.rsna.org 689

Table 2 Cancer Stage according to Year of Diagnosis in Women Aged 75 Years and Older with Stage 0 IV Cancer (n = 1162) Cancer Stage 1990 1994 (n = 120) Figure 3 1995 1999 (n = 225) Figure 3: Graph shows the change in stage over time (1990 2011) for breast cancer cases in patients aged 75 years and older (n = 1162). 85 years and older were also less likely to undergo surgery and less likely to undergo radiation therapy or chemotherapy than younger women 75 84 years of age (Table 5). Of the PtD and PhysD cases, there was no difference in the 2000 2004 (n = 339) 2005 2009 (n = 359) 2010 2011 (n = 119) 0 4 (3) 17 (8) 48 (14) 61 (17) 21 (18) I 59 (49) 132 (59) 176 (52) 173 (48) 58 (49) II 33 (28) 48 (21) 78 (23) 91 (25) 24 (20) III 21 (18) 21 (9) 32 (9) 30 (8) 12 (10) IV 3 (2) 7 (3) 5 (2) 4 (1) 4 (3) Note. Data are numbers of patients. Numbers in parentheses are percentages. Table 3 Detection Method according to Year of Diagnosis in Women Aged 75 Years and Older with Stage I IV Cancer (n = 1011) Diagnosis Year No. of Patients with PtD or PhysD Cancer (n = 406) 1990 1994 61 (53) 55 (47) 1994 1999 95 (46) 113 (54) 2000 2004 106 (36) 185 (64) 2005 2009 109 (37) 189 (63) 2010 2011 35 (36) 63 (64) Note. Numbers in parentheses are percentages. No. of Patients with MamD Cancer (n = 605) rate of mammographically occult cancers (not seen on mammograms subsequent to presentation with a physical finding) by age (13% of cases detected by a patient or physician [55 of 418 patients]) (Table 5). Table 4 Forward Logistic Regression Model for MamD Breast Cancer according to Order of Entry into the Model in Women Aged 75 94 Years (n = 1162) Variable Odds Ratio TNM stage 0 17.29 (7.57, 39.49) TNM stage I 5.94 (4.46, 7.91) TNM stage II, III, and IV Reference category Estrogen receptor 2.69 (1.69, 4.27) positive Diagnosis year 1.98 (1.46, 2.69) 2000 2011 Diagnosis year Reference category 1990 1999 Age 75 84 compared 1.59 (1.06, 2.38) with 85 94 Note. Numbers in parentheses are 95% CIs. Reference category indicates the category of the variable used to calculate the odds ratio. Patients with stage I III MamD invasive breast cancer were 31% more likely to be treated with lumpectomy (87% [524 of 603 patients]) than were patients with PtD or PhysD cancer (56% [217 of 385 patients]) and were 28% less likely to undergo mastectomy (13% [79 of 603 patients]) than were patients with PtD or PhysD cancer (42% [160 of 385 patients]) (P,.001) (Table 6). Patients with stage I III MamD breast cancer were 20% more likely to undergo surgery with radiation treatment (84% [509 of 603 patients]) than were patients with PtD or PhysD cancer (64% [245 of 385 patients]) and were 11% less likely to undergo adjuvant chemotherapy treatment (6% [36 of 603 patients]) than patients with PtD or PhysD cancer (17% [64 of 385 patients]) (Table 6). Survival Analysis Mean follow-up time for stage I III invasive breast cancer cases during 1990 2010 was 7.3 years (median, 6.41 years; range, 1.8 21.0 years; n = 946). For stage I III invasive breast cancer in patients 75 years and older, relapse-free survival was significantly better among the MamD cases (5-year relapse-free survival: 96% for patients with MamD cancer vs 87% 690 radiology.rsna.org n Radiology: Volume 273: Number 3 December 2014

Table 5 Detection Method and Diagnostic Characteristics in Women Aged 75 79 Years, 80 84 Years, and 85 Years and Older with All Stages of Cancer (n = 1162) Parameter 75 79 Years (n = 618) for patients with PtD or PhysD cancer; log-rank test = 18.62; P,.001) (Fig 4). Breast cancer disease-specific 5-year survival was superior for patients who had MamD cancer, with 97% 5-year disease-specific survival versus 87% for patients with PtD or PhysD cancer (logrank test = 17.81; P,.001) (Fig 5). Overall 5-year survival for patients with MamD breast cancer was 85%, as opposed to 67% for patients with PtD or PhysD cancer (log-rank test = 22.47, P,.001) (Fig 6). In a Cox proportional hazards regression model, mammography detection was significantly associated with decreased breast cancer mortality (stage I III) (hazard ratio = 0.50; 95% confidence interval [CI]: 0.31, 0.82; P,.001) adjusted for age and treatment (surgery, chemotherapy, radiation 80 84 Years (n = 390) 85 94 Years (n = 154) P Value Detection method Mammography 411 (67) 248 (64) 85 (55).032 Patient or physician 207 (33) 142 (36) 69 (45) TNM stage 0 81 (13) 54 (14) 16 (10).558 I 320 (52) 201 (52) 77 (50) II 139 (23) 95 (24) 40 (26) III 69 (11) 30 (8) 17 (11) IV 9 (1) 10 (2) 4 (2) Surgery type None 4 (1) 9 (2) 7 (4).011 Lumpectomy 463 (75) 294 (75) 115 (75) Mastectomy 151 (24) 87 (22) 32 (21) Radiation administered 537 (87) 315 (81) 119 (77).003 Chemotherapy administered 75 (12) 25 (6) 8 (5).002 Follow-up status Alive with no evidence of disease 330 (53) 202 (52) 63 (41).073 Alive with this cancer 6 (1) 3 (1) 3 (2) Alive with other cancer 5 (1) 3 (1) 1 (1) Died with no evidence of disease 161 (26) 130 (33) 62 (40) Died with this cancer 53 (9) 28 (7) 12 (8) Died with other cancer 41 (7) 19 (5) 10 (6) PtD and PhysD cancers not seen at subsequent mammography (mammographically occult) (n = 418) 32 (16) [32/207] 15 (11) [15/142] 8 (12) [8/69].106 Note. Data are number of patients, unless indicated otherwise. Numbers in parentheses are percentages. Numbers in brackets are data used to calculate percentages. therapy, and aromatase inhibitors). In the model adjusted for age only, mammography detection was also associated with decreased breast cancer mortality (hazard ratio = 0.38; 95% CI: 0.24, 0.61; P,.001). Conversely, the risk of breast cancer mortality among the patients with PtD and PhysD cancers was 2.62, corrected for age only, and 1.98, corrected for age and treatment (age only: hazard ratio = 2.62; 95% CI: 1.65, 4.16; P,.001) (age and treatment corrected: hazard ratio = 1.98; 95% CI: 1.22, 3.22; P,.001). Discussion Given the dearth of evidence regarding mammography screening in women 75 years and older, we evaluated presentation, treatment, and outcome differences between MamD breast cancer and PtD and PhysD cancer in our institutional cohort of breast cancer cases. We observed a significant increase in MamD breast cancer and a decrease in PtD and PhysD breast cancer over a 21-year time period. The observed increase in MamD breast cancer coincides with the 20% increase in women 75 years and older reporting a mammography examination in the past 2 years during the period of 1990 to 2010 in the United States (24). Over time, from 1990 to 2011, we observed a significant shift to lowerstage disease incidence, with a decrease in stage II and III breast cancer that was concordant with the observed increase in MamD breast cancer and the decrease in PtD and PhysD breast cancer. Unlike our previous study of women 40 49 years of age in which we observed a stage shift with a decrease in stage III breast cancer, in the group 75 years and older, we observed a decrease in stage II and III breast cancer with increased mammography detection (23). Possible explanations of the stage shift difference could be reduced breast density with older age, a lower rate of participation in regular screening with older age, or the absence of a sufficient sample size to detect a reliable percentage of difference in stage over time. An association between mammography screening programs and similar downstaging of breast carcinomas in older women has previously been documented and reported (25 28). Downstaging of breast cancer is particularly critical among women 75 years and older because early-stage lesions are associated with improved prognosis and are potentially treatable without chemotherapy in a group with higher rates of comorbidity and general lack of resilience for such treatment (13,29). In a recent study by Webb et al, they reported that breast cancer deaths at all ages occur most often among women who have not undergone screening with mammography (30). McCarthy et al also reported that older women who undergo regular mammography screening are less likely to die of breast cancer Radiology: Volume 273: Number 3 December 2014 n radiology.rsna.org 691

Table 6 Treatment and Outcome Characteristics according to Detection Method for Invasive Stage I III Breast Cancer in Women Aged 75 Years and Older (n = 988) Variable Figure 4 Figure 4: Graph shows relapse-free survival according to detection method for invasive breast cancer cases in patients aged 75 years and older (n = 946) (logrank test = 18.62, P,.001). Pt/PhysD = detection by patient or physician. (31). In our study, patients with MamD invasive breast cancer cases had significantly better 5-year disease-specific survival than those with PtD and PhysD breast cancers, which is most likely No. of Patients with PtD and PhysD Cancer (n = 385) No. of Patients with MamD Cancer (n = 603) P Value Surgery type None 8 (2) 0 (0),.001 Lumpectomy 217 (56) 524 (87) Mastectomy 160 (42) 79 (13) Therapy administered Surgery only 67 (17) 57 (9),.001 Hormone treatment only 6 (1.6) 0 Chemotherapy only 1 (0.2) 0 Radiation only 1 (0.2) 0 Surgery and radiation therapy 247 (64) 509 (84) Surgery and chemotherapy 12 (3) 8 (1) Surgery, radiation therapy, 52 (14) 28 (5) and chemotherapy TNM stage I 139 (36) 459 (76),.001 II 153 (40) 121 (20) III 93 (24) 23 (4) Note. Data are number of patients, unless indicated otherwise. Numbers in parentheses are percentages. the effect of fewer late-stage cancers. The Cox regression model, corrected for treatment, confirms the significant association of mammography detection with improved disease-specific survival. Schonberg et al observed worse survival in older women who received a diagnosis of stage II and higher breast cancer, most likely due to lack of tolerable treatment options (32). Our observed invasive breast cancer disease-specific survival rates among patients with MamD cancers and those with PtD and PhysD cancers were 97% and 87%, respectively; these are distinctly superior to the poor disease-specific survival rates reported among women aged 75 79 years (76%) and 80 years and older (70%) in the United Kingdom (33). In the United Kingdom, women over the age of 70 are not invited to undergo screening and receive decreased surgical and radiation treatment with age, which may account for the poor rates of diseasespecific survival (34, 35). Women 75 years of age and older in the Women s Health Initiative with intervals longer than 2 years between mammograms or no mammograms had significantly increased hazard of breast cancer death, indicating a screening benefit in this age group (36). The lower rate of MamD breast cancer among women aged 85 and older compared with the 75- to 79-yearolds and the 80- to 84-year-olds may be a result of reduced participation in screening due to reduced life expectancy and comorbid conditions. Breast cancer is the second leading cause of cancer death in women aged 80 years and older (8), but women aged 85 years and older may not have sufficient life expectancy to warrant participation in mammography screening programs. DCIS associated with mammography detection was less likely among patients 75 years and older than that reported in younger patients (28). While the rate of DCIS increased with mammography use, DCIS may not present as great a risk for progression or recurrence in the elderly, who have reduced life expectancy, and can often be safely treated with surgery and radiation (37,38). When discussing mammography screening options after the age of 75, our results indicate that women should be informed of the possible benefit of 692 radiology.rsna.org n Radiology: Volume 273: Number 3 December 2014

Figure 5 Figure 5: Graph shows disease-specific survival according to detection method for invasive breast cancer cases in patients aged 75 years and older (n = 946) (log-rank test = 17.81, P,.001). Pt/PhysD = detection by patient or physician. Figure 6 trial or an evaluation of a mammography screening program, which restricts our ability to make recommendations concerning mammography screening. We do not know if patients participated in mammography screening programs, underwent routine breast examination by a physician, examined their own breasts regularly, or had interval cancers, in the case of PtD and PhysD cancers. Our study population was relatively homogeneous (primarily white race) and may not be generalizable to a more diverse population. The county in which our institution is located has relatively high access to mammography screening services, and more of our population may undergo screening than populations in other areas of the United States (39,40). In conclusion, in prior studies, investigators have noted that MamD breast cancers tend to be smaller and have better outcomes in women 70 74 years of age (41). In our study, MamD breast cancer among women 75 years and older was associated with earlier stage at diagnosis (smaller tumors), less extensive surgical and systemic therapy, and better disease-specific survival than PtD and PhysD breast cancer. These results indicate that the same benefits of early detection that is, less toxic treatment and improved survival obtained with mammography screening may apply to women aged 75 years and older (2 4). Disclosures of Conflicts of Interest: J.A.M. disclosed no relevant relationships. J.P. disclosed no relevant relationships. M.K.A. disclosed no relevant relationships. H.G.K. disclosed no relevant relationships. Figure 6: Graph shows overall survival according to detection method for invasive breast cancer cases in patients aged 75 years and older (n = 946) (logrank test = 22.47, P,.001). Pt/PhysD = detection by patient or physician. a decreased need for aggressive treatment and better disease-specific survival associated with early detection with mammography. A woman s personal health objectives, comorbid conditions, projected life expectancy, and tolerance for a possible false-positive result or treatment for breast cancer, if found, need to be taken into consideration (17). Future evaluation of mammography screening recommendations for women 75 years and older should include potential benefits of tolerable treatment associated with early detection, as well as reduction in breast cancer mortality. Limitations of our study include the fact that it was not a randomized clinical References 1. Surveillance Epidemiology and End Results. SEER Stat Fact Sheets: Breast. http://seer. cancer.gov/statfacts/html/breast.html. Accessed June 25, 2013. 2. US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. A Intern Med 2009;151(10):716 726, W-236. 3. Chen HH, Tabar L, Fagerberg G, Duffy SW. Effect of breast cancer screening after age 65. J Med Screen 1995;2(1):10 14. 4. Tabár L, Vitak B, Chen THH, et al. Swedish two-county trial: impact of mammographic Radiology: Volume 273: Number 3 December 2014 n radiology.rsna.org 693

screening on breast cancer mortality during 3 decades. Radiology 2011;260(3):658 663. 5. Smith RA, Duffy SW, Tabár L. Breast cancer screening: the evolving evidence. Oncology (Williston Park) 2012;26(5):471 475, 479 481, 485 486. 6. Arias E. United States life tables, 2008. Natl Vital Stat Rep 2012;61(3):1 64. 7. Stat Bite. Percent of US women who develop breast cancer over 10- and 20- year intervals according to their current age (2008 2010). J Natl Cancer Inst 2013;105(17):1261. 8. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63(1):11 30. 9. Yood MU, Owusu C, Buist DS, et al. Mortality impact of less-than-standard therapy in older breast cancer patients. J Am Coll Surg 2008;206(1):66 75. 10. Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med 2003;348(24):2431 2442. 11. Balakrishnan A, Ravichandran D. Early operable breast cancer in elderly women treated with an aromatase inhibitor letrozole as sole therapy. Br J Cancer 2011;105(12):1825 1829. 12. Kaplan HG, Malmgren JA, Atwood MK. Adjuvant chemotherapy and differential invasive breast cancer specific survival in elderly women. J Geriatr Oncol 2013;4(2):148 156. 13. Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 2013;31(19):2382 2387. 14. Sinclair N, Littenberg B, Geller B, Muss H. Accuracy of screening mammography in older women. AJR Am J Roentgenol 2011;197(5):1268 1273. 15. Braithwaite D, Zhu W, Hubbard RA, et al. Screening outcomes in older US women undergoing multiple mammograms in community practice: does interval, age, or comorbidity score affect tumor characteristics or false positive rates? J Natl Cancer Inst 2013;105(5):334 341. 16. Gross CP, Long JB, Ross JS, et al. The cost of breast cancer screening in the Medicare population. JAMA Intern Med 2013;173(3): 220 226. 17. Braithwaite D, Mandelblatt JS, Kerlikowske K. To screen or not to screen older women for breast cancer: a conundrum. Future Oncol 2013;9(6):763 766. 18. Schonberg MA, Breslau ES, McCarthy EP. Targeting of mammography screening accord- ing to life expectancy in women aged 75 and older. J Am Geriatr Soc 2013;61(3):388 395. 19. Hurria A. Cancer in older adults: the top five things oncologists need to know. B.J. Keedy Award and Lecture for Scientific Excellence in Geriatric Oncology. 2013 ASCO Aual Meeting. Presented June 3, 2013. 20. American Cancer Society. Breast Cancer: early detection. Recommendations for early breast cancer detection in women without breast symptoms. http://www. cancer.org/acs/groups/cid/documents/ webcontent/003165-pdf.pdf. Published February 6, 2013. Accessed June 26, 2013. 21. Edge SB, Burd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer-Verlag, 2010. 22. Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, contract no. N01-CN-67009, Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, Bethesda, MD. 23. Malmgren JA, Parikh J, Atwood MK, Kaplan HG. Impact of mammography detection on the course of breast cancer in women aged 40-49 years. Radiology 2012;262(3):797 806. 24. National Center for Health Statistics. Health, United States, 2012: with special feature on emergency care. Table 82. Hyattsville, Md: National Center for Health Statistics. 2013. 25. Solin LJ, Schultz DJ, Kessler HB, Hanchak NA. Downstaging of breast carcinomas in older women associated with mammographic screening. Breast J 1999;5(2):94 100. 26. Norman SA, Localio AR, Zhou L, et al. Benefit of screening mammography in reducing the rate of late-stage breast cancer diagnoses (United States). Cancer Causes Control 2006;17(7):921 929. 27. Ernster VL, Ballard-Barbash R, Barlow WE, et al. Detection of ductal carcinoma in situ in women undergoing screening mammography. J Natl Cancer Inst 2002;94(20):1546 1554. 28. Taplin SH, Ichikawa L, Buist DSM, Seger D, White E. Evaluating organized breast cancer screening implementation: the prevention of late-stage disease? Cancer Epidemiol Biomarkers Prev 2004;13(2):225 234. 29. Solin LJ, Legorreta A, Schultz DJ, Zatz S, Goodman RL. The importance of mammographic screening relative to the treatment of women with carcinoma of the breast. Arch Intern Med 1994;154(7):745 752. 30. Webb ML, Cady B, Michaelson JS, et al. A failure analysis of invasive breast cancer: Most deaths from disease occur in women not regularly screened. Cancer 2013 Sep 9. [Epub ahead of print] 31. McCarthy EP, Burns RB, Freund KM, et al. Mammography use, breast cancer stage at diagnosis, and survival among older women. J Am Geriatr Soc 2000;48(10):1226 1233. 32. Schonberg MA, Marcantonio ER, Ngo L, Li D, Silliman RA, McCarthy EP. Causes of death and relative survival of older women after a breast cancer diagnosis. J Clin Oncol 2011;29(12):1570 1577. 33. Ali AMG, Greenberg D, Wishart GC, Pharoah P. Patient and tumour characteristics, management, and age-specific survival in women with breast cancer in the East of England. Br J Cancer 2011;104(4):564 570. 34. National Cancer Intelligence Network. Breast cancer in the elderly NCIN data briefing. October 2010. http://www.ncin. org.uk/publications/data_briefings/breast_ cancer_elderly. Accessed June 25, 2014. 35. Bouchardy C, Rapiti E, Fioretta G, et al. Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Onc 2003;21:3580 3587. 36. Simon MS, Wassertheil-Smoller S, Thompson CA, et al. Mammography interval and breast cancer mortality in the Women s Health Initiative. Cancer Res 2013;73(8 Suppl): Abstract nr 157. 37. Kaplan HG, Malmgren JA. The breast cancer overdiagnosis conundrum: an oncologist s viewpoint. A Intern Med 2013;158(1):60 61. 38. Alvarado R, Lari SA, Roses RE, et al. Biology, treatment, and outcome in very young and older women with DCIS. A Surg Oncol 2012;19(12):3777 3784. 39. Elkin EB, Ishill NM, Snow JG, et al. Geographic access and the use of screening mammography. Med Care 2010;48(4):349 356. 40. Nickson C, Mason KE, Kavanagh AM. Breast cancer screening of women aged 70 74 years: results from a natural experiment across Australia. Breast Cancer Res Treat 2014; 143(2):367 372. 41. Understanding Breast Cancer: Mammography and Diagnostic Sites. Susan G. Komen Puget Sound Web site. http://www.komenpugetsound.org/understanding-breast-cancer/local-resources/mammography-and-diagnostic.html. Accessed September 9, 2013. 694 radiology.rsna.org n Radiology: Volume 273: Number 3 December 2014