Risk of Mortality by Histologic Type of Breast Cancer Among Women Aged 50 to 79 Years

ORIGINAL INVESTIGATION Risk of Mortality by Histologic Type of Breast Cancer Among Women Aged 50 to 79 Years

Christopher I. Li, MD, PhD; Roger E. Moe, MD; Janet R. Daling, PhD

Background: Recent studies suggest that the use of com- Results: Women with ILC had a risk of mortality 11% bined estrogen and progestin hormone replacement lower than women with IDC. The magnitude of this dif- therapy is associated with an increased risk of invasive ference has increased over the past 10 years and, from lobular carcinoma (ILC), but that it has little associa- 1994 through 1998, the risk of mortality was 26% lower tion with risk of invasive ductal carcinoma (IDC). Also, for women with ILC. Also, the risk of mortality was the incidence rates of ILC have risen over the past 10 years between 8% and 34% lower in women with mucinous while those of IDC have remained constant. Differences carcinoma, comedocarcinoma, or medullary, tubular, in survival rates by histologic types of tumor have been and papillary carcinomas compared with women with reported, but few of the published studies were popula- IDC. tion based or had adequate power to address this issue. Conclusions: Differences in prognosis by histologic type Methods: We conducted a retrospective cohort study of breast cancer were identified. The survival rate of spanning the years 1974 through 1998 using data from women 50 to 79 years old who have ILC, the cancer whose the 9 cancer registries that have participated in the Sur- histologic type is the most closely linked with the use of veillance, Epidemiology, and End Results Program since combined estrogen and progestin hormone replace- 1974. The cohort consisted of 164958 women aged 50 ment therapy, is more favorable than that of women with to 79 years who had been diagnosed as having 1 of 7 his- IDC and appears to be improving over time. tologic types of invasive breast cancer. Risks of mortality due to any cause were estimated using the Cox proportional hazards model. Arch Intern Med. 2003;163:2149-2153

GROWING number of stud- tect than IDC by mammographic or clini- ies have found that the cal examination.10 use of combined estrogen It is important to compare the prog- and progestin hormone noses associated with different histologic replacement therapy types of breast cancer if the conse- (CHRT)A is associated with a 2.0- to 3.9- quences of the changing incidence rates fold increase in the risk of developing in- of some breast cancers are to be under- vasive lobular carcinoma (ILC), the sec- stood. Differences in risks of mortality ac- ond most common histologic type of cording to histologic types have been iden- breast cancer, but that it has little impact tified; yet, results are conflicting and the on the risk of developing the most com- types considered “favorable” are subject mon histologic type, invasive ductal car- to debate.11 With respect to ILC, studies cinoma (IDC).1-5 Specifically, 4 of these show that its prognosis is better,12-14 the studies found no association between use same,15 or worse16,17 than that of IDC. of CHRT and ductal carcinoma,1-3,5 but 1 Other studies have evaluated less com- found that women who ever used CHRT mon histologic types, but the available evi- had a 43% increase in the risk of devel- dence suggests that mucinous,18-22 med- oping ductal carcinoma.4 Although it has ullary,23-25 and tubular17,26-28 histologic types From the Fred Hutchinson been reported that ILC represents only are associated with a risk of mortality Cancer Research Center, about 5% to 10% of all breast cancer greater or similar to that of IDC. How- Division of Public Health cases,6,7 incidence rates of ILC have risen ever, few of these studies were popula- Sciences, Seattle, Wash steadily in the United States from 1987 to tion based, and most were hampered by (Drs Li and Daling), and the 1995,8 and in 1999 ILC accounted for 16% relatively small numbers of cases of these Department of Surgery, School 9 of Medicine, University of of all invasive breast cancers. Alterna- rare histologic types of breast cancer. Washington, Seattle (Dr Moe). tively, IDC rates have remained essen- To further our knowledge of the mor- The authors have no relevant tially constant over the same time despite tality risks of breast cancer according to financial interest in this article. the fact that ILC is more difficult to de- histologic types, we conducted a popula-

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Downloaded From: https://jamanetwork.com/ on 09/28/2021 Table 1. Demographic, Carcinoma, and Treatment Characteristics of 164 958 Women Diagnosed as Having Breast Cancer Between 1974 and 1998

Histologic Type, No./Row %/Column %

Ductal Lobular Mucinous Comedocarcinoma Medullary Tubular Papillary Characteristic (n = 132 284) (n = 19 383) (n = 3923) (n = 3157) (n = 2902) (n = 2260) (n = 1049) Age, y 50-59 43 734/80.6/33.1 6153/11.3/31.7 747/1.4/19.0 1347/2.5/42.7 1305/2.4/45.0 757/1.4/33.5 209/0.4/19.9 60-69 48 615/80.6/36.8 7014/11.6/36.2 1367/2.3/34.8 1149/1.6/36.4 994/1.6/34.3 802/1.3/35.5 391/0.6/37.3 70-79 39 935/79.3/30.2 6216/12.3/32.1 1809/3.6/46.1 661/1.3/20.9 603/1.2/20.8 701/1.4/31.0 449/0.9/42.8 Mean (SD) 64.1 (8.3) 64.5 (8.4) 67.4 (8.0) 62.1 (8.0) 61.9 (8.1) 64.1 (8.5) 66.9 (8.0) Year of diagnosis (5-year groups) 1974-1978 17 836/83.2/13.5 1648/7.7/8.5 568/2.7/14.5 270/1.3/8.6 828/3.9/28.5 128/0.6/5.7 153/0.7/14.6 1979-1983 21 648/82.4/16.4 2507/9.5/12.9 544/2.1/13.9 481/1.8/15.2 703/2.7/24.2 227/0.9/10.0 167/0.6/15.9 1984-1988 28 754/82.3/21.7 3729/10.7/19.2 723/2.1/18.4 572/1.6/18.1 566/1.6/19.5 355/1.0/15.7 227/0.6/21.6 1989-1993 30 266/78.8/22.9 4730/12.3/24.4 971/2.5/24.8 1053/2.7/33.4 459/1.2/15.8 691/1.8/30.6 252/0.7/24.0 1994-1998 33 780/76.9/25.5 6769/15.4/34.9 1117/2.5/28.5 781/1.8/24.7 346/0.8/11.9 859/2.0/38.0 250/0.6/23.8 Follow-up time, y Ͻ1 14 107/79.9/10.7 2425/13.7/12.5 368/2.1/9.4 211/1.2/6.7 203/1.2/7.0 259/1.5/11.5 75/0.4/7.1 1-3 25 645/80.8/19.4 3895/12.3/20.1 673/2.1/17.2 504/1.6/16.0 450/1.4/15.5 425/1.3/18.8 153/0.5/14.6 3-5 20 967/79.9/15.8 3262/12.4/16.8 577/2.2/14.7 586/2.2/18.6 340/1.3/11.7 367/1.4/16.2 152/0.6/14.5 5-10 36 233/79.6/27.4 5425/11.9/28.0 1128/2.5/28.8 1041/2.3/33.0 649/1.4/22.4 700/1.5/31.0 318/0.7/30.3 Ͼ10 35 332/80.6/26.7 4376/10.0/22.6 1177/2.7/30.0 815/1.9/25.8 1260/2.9/43.4 509/1.2/22.5 351/0.8/33.5 Mean (SD) 7.0 (5.6) 6.4 (5.3) 7.6 (5.8) 7.3 (5.3) 9.5 (6.8) 6.7 (5.3) 8.2 (5.9) Registry Atlanta 9494/7.2/81.4 1342/6.9/11.5 248/6.3/2.1 213/6.7/1.8 146/5.0/1.3 126/5.6/1.1 88/8.4/0.8 Connecticut 23 729/17.9/82.7 2935/15.1/10.2 614/15.7/2.1 476/15.1/1.7 498/17.2/1.7 268/11.9/0.9 157/15.0/0.5 Detroit 22 162/16.8/78.4 3693/19.1/13.1 582/14.8/2.1 687/21.8/2.4 633/21.8/2.2 318/14.1/1.1 192/18.3/0.7 Hawaii 5552/4.2/83.9 511/2.6/7.7 181/4.6/2.7 124/3.9/1.9 114/3.9/1.7 86/3.8/1.3 52/5.0/0.8 Iowa 17 306/13.1/80.5 2313/11.9/10.8 574/14.6/2.7 424/13.4/2.0 487/16.8/2.3 273/12.1/1.3 124/11.8/0.6 New Mexico 6619/5.0/80.2 1057/5.5/12.8 204/5.2/2.5 76/2.4/0.9 111/3.8/1.3 118/5.2/1.4 63/6.0/0.8 San Francisco-Oakland 22 571/17.1/79.3 3718/19.2/13.1 676/17.2/2.4 562/17.8/2.0 399/13.7/1.4 405/17.9/1.4 147/14.0/0.5 Seattle 18 494/14.0/78.3 3015/15.6/12.8 640/16.3/2.7 409/13.0/1.7 336/11.6/1.4 562/24.9/2.4 159/15.2/0.7 Utah 6357/4.8/80.5 799/4.1/10.1 204/5.2/2.6 186/5.9/2.4 178/6.1/2.3 104/4.6/1.3 67/6.4/0.8 Race/ethnicity Non-Hispanic white 112 945/85.4/79.9 17 308/89.3/12.2 3298/84.1/2.3 2592/82.1/1.8 2323/80.0/1.6 2042/90.4/1.4 784/74.7/0.6 Black 8749/6.6/80.8 952/4.9/8.8 278/7.1/2.6 287/9.1/2.7 340/11.7/3.1 75/3.3/0.7 146/13.9/1.3 American Indian 256/0.2/79.0 31/0.2/9.6 10/0.3/3.1 11/0.3/3.4 12/0.4/3.7 1/0.0/0.3 3/0.3/0.9 Asian/Pacific Islander 5600/4.2/84.5 434/2.2/6.5 186/4.7/2.8 156/4.9/2.4 120/4.1/1.8 55/2.4/0.8 76/7.2/1.1 Hispanic white 3466/2.6/80.3 483/2.5/11.2 114/2.9/2.6 81/2.6/1.9 83/2.9/1.9 57/2.5/1.3 30/2.9/0.7 Other/unknown 1268/1.0/80.6 175/0.9/11.1 37/0.9/2.4 30/1.0/1.9 24/0.8/1.5 30/1.3/1.9 10/1.0/0.6 Stage Localized 77 086/78.0/59.4 11 426/11.6/59.9 3314/3.4/86.1 2344/2.4/75.1 1747/1.8/61.2 2014/2.0/90.4 851/0.9/82.5 Regional 45 813/83.3/35.3 6640/12.1/34.8 447/0.8/11.6 700/1.3/22.4 1030/1.9/36.1 202/0.4/9.1 154/0.3/14.9 Distant 6918/84.3/5.3 1009/12.3/5.3 88/1.1/2.3 77/0.9/2.5 78/1.0/2.7 13/0.2/0.6 26/0.3/2.5 Missing 2467 308 74 36 47 31 18 Surgical treatment Performed 428/85.3/0.3 49/9.8/0.3 12/2.4/0.3 5/1.0/0.2 2/0.4/0.1 2/0.4/0.1 4/0.8/0.4 Not performed 122 172/80.3/99.7 17 478/11.5/99.7 3621/2.4/99.7 3010/2.0/99.8 2793/1.8/99.9 2057/1.4/99.9 979/0.6/99.6 Missing 9684 1856 290 142 107 201 66 Radiation therapy None 87 170/79.7/66.9 13 183/12.1/68.9 2647/2.4/68.5 2262/2.1/72.5 2045/1.9/72.2 1268/1.2/56.8 790/0.7/76.4 Treated 43 067/81.1/33.1 5942/11.2/31.1 1215/2.3/31.5 859/1.6/27.5 789/1.5/27.8 965/1.8/43.2 244/0.5/23.6 Missing 2047 258 61 36 68 27 15

tion-based retrospective cohort study of women diag- participating in the National Cancer Institute’s SEER Program. nosed as having breast cancer in 9 population-based Sur- We restricted our study to women 50 to 79 years old because the veillance, Epidemiology, and End Results (SEER) cancer risk factors and outcomes of breast cancer differ by age and, par- 29 registries from 1974 to 1998. ticularly, menopausal status. The SEER registries that were used serve Connecticut, Hawaii, Iowa, New Mexico, Utah, and the urban areas surrounding Atlanta, Ga; Detroit, Mich; San Francisco- METHODS Oakland, Calif; and Seattle, Wash. Patients’ medical records are the principal sources of data used by SEER. It is estimated that Women 50 to 79 years old and diagnosed as having a primary more than 95% of all incident cancer cases in the populations un- invasive breast cancer between January 1974 and December 1998 der surveillance are ascertained. Further operational details and were identified through 9 population-based US cancer registries methods used by the SEER Program are provided elsewhere.30

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Downloaded From: https://jamanetwork.com/ on 09/28/2021 The 188701 women diagnosed for the first time with invasive breast cancer were eligible for this study. They were Table 2. Multivariate-Adjusted Risks of Mortality grouped according to the histologic categories of their tumors by Histologic Type of Carcinoma* as defined by the International Classification of Diseases for On- cology (ICD-O) codes: ductal (ICD-O code 8500), lobular (8520 Patients Alive, No. (%) and 8522), mucinous (8480), comedocarcinoma (8501), medullary (8510), tubular (8211 and 8201), and papillary (8050 Carcinoma Yes No HR (95% CI) and 8503). The 23743 women who were assigned other ICD-O Ductal 77 637 (58.7) 54 647 (41.3) 1.00 (Reference) codes, and represented 12.6% of eligible subjects, were ex- Lobular 12 988 (67.0) 6395 (33.0) 0.89 (0.86-0.91) cluded from our analysis, leaving a total of 164958 women. Mucinous 2563 (65.3) 1360 (34.7) 0.80 (0.76-0.85) In addition to age at diagnosis, year of diagnosis, and histo- Comedocarcinoma 2219 (70.3) 938 (29.7) 0.92 (0.86-0.98) logic type, SEER data from 1974 to 1998 also include informa- Medullary 1602 (55.2) 1300 (44.8) 0.82 (0.78-0.87) tion on SEER historic stage (localized, regional, or distant) and Tubular 1841 (81.5) 419 (18.5) 0.66 (0.60-0.73) race/ethnicity. Also, data on first courses of surgical and radia- Papillary 659 (62.8) 390 (37.2) 0.81 (0.73-0.90) tion treatments are available, but data on adjuvant chemotherapy and hormonal therapy are not. While information on mari- Abbreviations: CI, confidence interval; HR, hazard ratio; SEER, Surveillance, Epidemiology, and End Results Program. tal status is provided, data regarding other sociodemographic *All HRs are adjusted for diagnosis age, year of diagnosis, SEER historic factors, such as income and health insurance status, are not. stage, SEER registry, surgical treatment, and radiation therapy. Information on survival is obtained annually by each registry through a variety of data sources including hospital cancer registries and discharge data sets, the Department of Mo- cases of ILC were diagnosed in Hawaii (7.7% of the total tor Vehicles registration files, regional records of the Health Care cases) while relatively more were diagnosed in Detroit and Financing Administration, voters’ registration records, death San Francisco-Oakland (13.1%). Multiple differences by records, and the Social Security death index. In addition to vi- race/ethnicity were also seen, as relatively more cases of ILC tal status, SEER also provides survival time for each patient. It and fewer cases of comedocarcinoma were observed among is calculated in months using the date of diagnosis and which- non-Hispanic whites, and the opposite was true for black, ever of the following occurred first: (1) date of death, (2) date last known to be alive, or (3) December 31, 1998, the fol- Asian/Pacific Islander, and American Indian women. Lo- low-up cutoff date used in our analysis. calized disease was more common among women with tu- Associations between histologic types of breast cancer and bular, mucinous, and papillary carcinomas (90.4%, 86.1%, risks of mortality due to any cause were estimated using the and 82.5%, respectively) and less common among women Cox proportional hazards model.31 Using Stata 7.0 for Win- with IDC and ILC (59.4% and 59.9%, respectively). More dows (Stata Corp, College Station, Tex) statistical software, the than 99.6% of women with tumors of any histologic type Cox regression was performed to compute hazard ratios (HRs) received surgical treatment. Finally, a first course of treat- and 95% confidence intervals (CIs) and to evaluate the effects ment with radiation was the most common for women with of modifying factors. In our final multivariate models we ad- papillary carcinomas (76.4%) and the least common for justed for age at diagnosis (continuous data), year of diagnosis women with tubular carcinomas (56.8%). (continuous), SEER historic stage (categorical), SEER registry Table 2 (categorical), and whether surgical and/or radiation breast can- presents risks of mortality due to any cause cer therapy was used as a first-course treatment, because each associated with different histologic types of breast can- was hypothesized as a potential confounder. We found that year cer adjusted for age at diagnosis, year of diagnosis, SEER of diagnosis and SEER registry were effect modifiers, and thus historic stage, SEER registry, surgical treatment, and ra- we performed analyses stratified by 5-year categories of diag- diation therapy. Compared with women with IDC, women nosis year (1974-1978, 1979-1983, 1984-1988, 1989-1993, and with ILC had an 11% reduction (95% CI, 9%-14%) in their 1994-1998) and by SEER registry. risk of mortality. Reductions in risk of mortality were also observed for women with each of the other histologic types RESULTS of cancer, and women with tubular carcinomas had a 34% reduction, the largest reduction observed for any of the The cohort of 164958 women had 132284 ductal (80.2%), histologic types. 19383 lobular (11.8%), and 3923 mucinous carcinomas While reductions in risk of mortality were generally (2.4%); 3157 comedocarcinomas (1.9%); and 902 medul- observed for each category of diagnosis year for each his- lary (1.8%), 2260 tubular (1.4%), and 1049 papillary car- tologic type, many of these reductions were within the lim- cinomas (0.6%). Table 1 presents a comparison of vari- its of chance (Table 3). Some variations in the magni- ous characteristics by histologic type. Women with tude of these risks were observed over time. Specifically, medullary carcinomas and comedocarcinomas had the low- the risk of mortality associated with ILC decreased over the est mean ages at diagnosis (61.9 and 62.1 years, respec- past 10 years, so that between 1994 and 1998, the risk of tively), while women with mucinous and papillary carci- mortality was 26% lower for women with ILC than for nomas had the highest mean ages at diagnosis (67.4 and women with IDC. Also, the risk of mortality associated with 66.9 years, respectively). The number of cases classified as mucinous carcinoma was reduced by 31% compared with medullary carcinoma decreased over the course of the study, the risk associated with IDC between 1994 and 1998, the while the number of cases classified as each of the other greatest reduction for mucinous carcinoma observed in any types generally increased. The mean follow-up time was of the 5-year periods evaluated. Alternatively, while women longest for women with medullary and papillary carcino- with medullary and papillary carcinomas experienced de- mas (9.5 and 8.2 years, respectively), and shortest for creased risks of mortality between 1974 and 1993, this re- women with ILC (6.4 years). Numerous differences by SEER duction was no longer observed during the most recent pe- registry were also observed. For example, relatively fewer riod, 1994 to 1998.

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Downloaded From: https://jamanetwork.com/ on 09/28/2021 Table 3. Multivariate-Adjusted Risks of Mortality by Histologic Type of Carcinoma Stratified by Year of Diagnosis (5-Year Groups)*

Hazard Ratio (95% Confidence Interval)

Carcinoma 1974-1978 1979-1983 1984-1988 1989-1993 1994-1998 Ductal (reference) 1.00 1.00 1.00 1.00 1.00 Lobular 0.92 (0.86-0.98) 0.92 (0.87-0.97) 0.93 (0.88-0.98) 0.81 (0.76-0.86) 0.74 (0.67-0.82) Mucinous 0.81 (0.73-0.89) 0.83 (0.75-0.93) 0.82 (0.72-0.92) 0.79 (0.69-0.91) 0.69 (0.52-0.91) Comedocarcinoma 1.03 (0.89-1.20) 0.85 (0.74-0.96) 0.81 (0.70-0.93) 0.95 (0.83-1.09) 0.95 (0.73-1.23) Medullary 0.81 (0.75-0.89) 0.86 (0.77-0.95) 0.75 (0.65-0.87) 0.87 (0.71-1.06) 1.17 (0.81-1.70) Tubular 0.63 (0.49-0.81) 0.67 (0.56-0.82) 0.77 (0.64-0.92) 0.70 (0.57-0.85) 0.48 (0.32-0.73) Papillary 0.74 (0.61-0.91) 0.87 (0.72-1.06) 0.80 (0.66-0.99) 0.80 (0.61-1.05) 1.00 (0.63-1.59)

*All hazard ratios are adjusted for diagnosis age, SEER (Surveillance, Epidemiology, and End Results Program) historic stage, SEER registry, surgical treatment, and radiation therapy.

Table 4. Multivariate-Adjusted Risks of Mortality by Histologic Type of Carcinoma Stratified by SEER Registry*

Hazard Ratio (95% Confidence Interval)

Carcinoma Atlanta Connecticut Detroit Hawaii Iowa Ductal (reference) 1.00 1.00 1.00 1.00 1.00 Lobular 0.89 (0.80-0.99) 0.86 (0.80-0.92) 0.88 (0.83-0.93) 0.71 (0.59-0.85) 0.93 (0.86-0.99) Mucinous 0.63 (0.49-0.80) 0.82 (0.72-0.94) 0.83 (0.72-0.95) 0.94 (0.71-1.26) 0.85 (0.74-0.97) Comedocarcinoma 0.93 (0.72-1.20) 0.89 (0.74-1.06) 0.91 (0.79-1.04) 0.92 (0.63-1.33) 0.99 (0.82-1.18) Medullary 0.65 (0.49-0.87) 0.83 (0.72-0.95) 0.76 (0.67-0.86) 0.95 (0.70-1.30) 0.83 (0.73-0.95) Tubular 0.70 (0.46-1.08) 0.62 (0.46-0.83) 0.61 (0.47-0.77) 0.42 (0.21-0.84) 0.65 (0.50-0.84) Papillary 0.93 (0.65-1.33) 0.84 (0.65-1.07) 0.72 (0.56-0.91) 1.24 (0.72-2.15) 0.78 (0.59-1.03)

New Mexico San Francisco-Oakland Seattle Utah Ductal (reference) 1.00 1.00 1.00 1.00 Lobular 0.84 (0.75-0.95) 0.94 (0.88-0.99) 0.85 (0.79-0.91) 0.96 (0.84-1.10) Mucinous 0.83 (0.64-1.08) 0.76 (0.66-0.87) 0.83 (0.72-0.96) 0.78 (0.60-1.01) Comedocarcinoma 0.82 (0.50-1.35) 1.00 (0.86-1.17) 0.84 (0.70-1.01) 0.87 (0.66-1.14) Medullary 0.81 (0.60-1.09) 0.87 (0.74-1.01) 0.86 (0.73-1.02) 0.89 (0.70-1.14) Tubular 0.60 (0.37-0.99) 0.70 (0.56-0.86) 0.67 (0.53-0.83) 1.12 (0.78-1.60) Papillary 0.59 (0.35-0.98) 0.87 (0.66-1.14) 0.98 (0.76-1.28) 0.58 (0.37-0.91)

*All hazard ratios are adjusted for diagnosis age, year of diagnosis, SEER (Surveillance, Epidemiology, and End Results Program) historic stage, surgical treatment, and radiation therapy.

Some variations by SEER registry were also ob- tries evaluated, which supported our study’s generaliz- served (Table 4). Compared with women having IDC, ability. women with ILC had a 7% to 29% decrease in risk of mor- Another concern is that we lacked information re- tality in all registries except Utah’s. Additionally, regarding certain potential confounders, including hor- duced risks of death that were not within the limits of monal, reproductive, anthropometric, and lifestyle fac- chance were observed for mucinous, medullary, tubu- tors, that may be associated with histologic type of cancer lar, and papillary tumors in 6, 4, 7, and 3 of the 9 regis- and survival time. In addition, we lacked data on other treat- tries, respectively. ments, such as hormonal therapy and chemotherapy, that study subjects may have received. These treatments are COMMENT known to improve survival time, and it is likely that their administration also differs by histologic type of cancer, mak- A limitation of this study is that the classification of ing them important potential confounders. For example, tumors by histologic type was not conducted in a cen- it has been reported that lobular tumors are more likely than tralized location, and that histopathologic definitions of ductal tumors to be hormone receptor–positive,32 and thus tumors have changed over time. What is somewhat are more likely to be candidates for hormonal treatment, reassuring, however, is that our results are concordant ie, treatment with with tamoxifen. Thus, the risk of mor- with other published results; and when we stratified by tality associated with ILC may be decreasing as tamoxifen year of diagnosis, the directions of the risks we use, which reduces mortality due to hormone receptor– observed were fairly consistent over time. Furthermore, positive breast cancer,33 is increasing. statistically significant reductions in risks of mortality Although patterns of use of tamoxifen and chemo- associated with lobular, mucinous, and tubular carcino- therapy for breast cancer changed over the study period, mas were observed in 6 or more of the 9 cancer regis- our data suggest that, in particular, lobular, mucinous, and

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Downloaded From: https://jamanetwork.com/ on 09/28/2021 tubular carcinomas were and continue to be associated with rate of invasive lobular breast carcinoma among older women. Cancer. 2000; lower risks of mortality than IDC, and that the magnitude 88:2561-2569. 9. Surveillance, Epidemiology, and End Results (SEER) Program Public-Use Data of this lower risk has increased over time as ILC was as- (1973-1999). Bethesda, Md: Division of Cancer Control and Population Sci- sociated with an 8% lower risk of mortality compared with ences, Surveillance Research Program, Cancer Statistics Branch, National Can- IDC between 1974 and 1983, and a 24% lower risk be- cer Institute; April 2002. tween 1994 and 1998. Given that since 1987 ILC inci- 10. Dixon J, Anderson T, Page D, Lee D, Duffy S. Infiltrating lobular carcinoma of the breast. Histopathology. 1982;6:149-161. dence rates have increased steadily in the United States 11. Bush TL, Whiteman MK. Hormone replacement therapy and risk of breast can- among women older than 50 years, while IDC incidence cer. JAMA. 1999;281:2140-2141. rates have held constant since 1987, this finding is par- 12. DiConastanzo D, Rosen PP, Gareen I, Franklin S, Lesser M. Prognosis of infiltrat- ticularly important.7 Furthermore, there is a growing body ing lobular carcinoma: an analysis of “classical” and “variant” tumors. Am J Surg of evidence linking the use of CHRT to an elevated risk of Pathol. 1990;14:12-23. 1-5 13. Du Toit RS, Locker AP, Ellis IO, et al. An evaluation of differences in prognosis, ILC. Recent data from the Women’s Health Initiative ran- recurrence patterns and receptor status between invasive lobular and other in- domized trial comparing CHRT to placebo indicates that vasive carcinomas of the breast. Eur J Surg Oncol. 1991;17:251-257. CHRT use is associated with an increased risk of breast can- 14. Toikkanen S, Pylkkanen L, Joensuu H. Invasive lobular carcinoma of the breast cer.34 While the Women’s Health Initiative investigators have has better short- and long-term survival than invasive ductal carcinoma. Br J Can- cer. 1997;76:1234-1240. not reported on whether this risk differs by histologic type, 15. Sastre-Garau X, Jouve M, Asselain B, et al. Infiltrating lobular carcinoma of the 5 case-control studies have shown that the risk of breast breast: clinicopathologic analysis of 975 cases with reference to data on con- cancer associated with CHRT use varies by histologic type. servative therapy and metastatic patterns. Cancer. 1996;77:113-120. All 5 studies found that current or recent use of CHRT in- 16. Ashikari R, Huvos A, Urban J, Robbins GF. Infiltrating lobular carcinoma of the creased the risk of ILC 2.0- to 3.9-fold, while only 1 found breast. Cancer. 1973;31:110-116. 4 17. Mate TP, Carter D, Fisher DB, et al. A clinical and histopathologic analysis of the that it also increased the risk of IDC. Considered along results of conservative surgery and radiation therapy in stage I and II breast car- with results from this study, it appears that the types of breast cinoma. Cancer. 1986;58:1995-2002. carcinomas CHRT users have a greater risk of developing, 18. Fentiman IS, Millis RR, Smith P, Ellul JP, Lampejo O. Mucoid breast carcino- such as ILC, have a relatively favorable prognosis. How- mas: histology and prognosis. Br J Cancer. 1997;75:1061-1065. 19. Tabar L, Fagerberg G, Chen HH, Duffy SW, Gad A. Tumour development, histol- ever, further studies are needed and we encourage inves- ogy and grade of breast cancers: prognosis and progression. Int J Cancer. 1996; tigators assessing the relationship between CHRT use and 66:413-419. breast cancer incidence to stratify their analyses by histo- 20. Toikkanen S, Eerola E, Ekfors TO. Pure and mixed mucinous breast carcinomas: logic type. DNA stemline and prognosis. J Clin Pathol. 1988;41:300-303. 21. 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