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Trends in breast cancer presentation and care according to age in a single institution
The American Journal of Surgery 188 (2004) 437– 439
Scientific paper
Trends in breast cancer presentation and care according to age in a single institution Doreen M. Agnese, M.D.a,*, Fouza Yusuf, M.P.H.b, John L. Wilson, Ph.D.b, Charles L. Shapiro, M.D.c, Amy Lehman, M.A.S.d, William E. Burak, Jr., M.D.a a
Division of Surgical Oncology, Department of Surgery, The Ohio State University, N924 Doan Hall, 410 W. 10th Ave., Columbus, OH 43210, USA b Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA c Department of Outcomes Management, The Ohio State University, Columbus, OH, USA d Center for Biostatistics, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA Manuscript received May 19, 2004; revised manuscript June 6, 2004 Presented at the Fifth Annual Meeting of the American Society of Breast Surgeons, March 31–April 4, 2004, Las Vegas, Nevada
Abstract Background: This study sought to determine the differences in presentation and treatment of young women (ⱕ40 years of age) with breast cancer. Methods: A prospective database was analyzed for differences in presentation and care in breast cancer patients ⱕ40 and ⬎40 years of age. Results: The study group consisted of 1685 women. Younger women were more likely to present with a palpable mass, have estrogen receptor/progesterone receptor (ER/PR)-negative tumors, and have more advanced disease at presentation. Although there was no difference in breast conservation rates, younger women were more likely to have postmastectomy reconstruction. Younger women were more likely to receive chemotherapy, even with node-negative tumors less than 1 cm in diameter (37% vs. 13%, P ⫽ 0.01). Conclusions: The presentation of younger women with breast cancer differs from that of older women. Although the surgical management is similar, adjuvant therapy differs, with younger women more likely to be treated with chemotherapy. © 2004 Excerpta Medica, Inc. All rights reserved. Keywords: Breast cancer; Young; Presentation; Therapy; Age
Breast cancer in young women is generally considered a more aggressive disease than that seen in older women. Numerous analyses have demonstrated a poorer prognosis in young women, even after controlling for stage at presentation [1,2]. The objective of this study was to determine the differences in presentation and treatment of young women (ⱕ40 years of age) with breast cancer. A prospective breast cancer database was established at the The Ohio State University in March 1998. All women diagnosed with breast cancer and receiving any portion of their treatment at The Ohio State University are entered into the database. This database was reviewed to identify all women diagnosed with breast cancer between March 1998 * Corresponding author. Tel.: ⫹1-614-293-6408; fax: ⫹1-614-2933465. E-mail address: [email protected]
and December 2002. The women with breast cancer identified during this interval were divided into two groups: those diagnosed at age ⱕ40 years, and those diagnosed at age ⬎40 years. Differences in presentation and treatment were sought. The variables analyzed included the mode of presentation, primary tumor characteristics, stage at diagnosis, and hormone receptor status. The primary operation, reconstructive surgery performed, and adjuvant therapy administered, including the type (chemotherapy or hormonal therapy) and duration of therapy, were also reviewed. Data relative to recurrence (local, regional, or distant) were also analyzed. Statistical analyses were performed using chisquare tests and logistic regression. Between March 1998 and December 2002, 1685 women were treated for breast cancer (ductal carcinoma-in-situ [DCIS] and invasive carcinoma) at The Ohio State University. One hundred sixty-three women were ⱕ40 and 1522
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved. doi:10.1016/j.amjsurg.2004.06.029
438
D.M. Agnese et al. / The American Journal of Surgery 188 (2004) 437– 439
Table 1 Differences in presentation and care of breast cancer in women ⱕ40 years of age Women ⱕ 40 n (%) Presentation with palpable mass DCIS Advanced stage (II, III, and IV) ER/PR positive Reconstruction after mastectomy Chemotherapy Chemotherapy for tumur ⬍1 cm (node negative) Hormonal therapy
Women ⬎ 40 n (%)
Table 2 Differences in recurrence after primary treatment for breast cancer in women ⱕ40
P
114 (70)
638 (42)
⬍0.0001
9 (6) 95 (67)
212 (16) 615 (45)
0.003 ⬍0.0001
88 (54) 48 (60)
971 (64) 193 (32)
0.02 ⬍0.0001
134 (82) 7 (37)
747 (49) 32 (13)
⬍0.0001 0.01
93 (57)
1088 (71)
0.0002
DCIS ⫽ ductal carcinoma-in-situ; ER/PR ⫽ estrogen receptor/progesterone receptor.
were ⬎40 years of age at the time of diagnosis. The results of this analysis are summarized in Table 1. Younger women were significantly more likely to present with a palpable mass (70% vs. 42%, P ⬍0.0001), and were more likely to have more advanced stage disease (II, III, and IV) at presentation (P ⬍0.0001). DCIS was seen less frequently in the younger population (P ⫽ 0.003). Fifty-four percent of the women ⱕ40 had estrogen receptor/progesterone receptor (ER/PR)-positive tumors compared with 64% of the women ⬎40 (P ⫽ 0.017). There was no difference in the rate of nodal positivity by size of the primary tumor between the groups. After controlling for stage of disease, there was no difference in the initial surgery performed (breast conservation vs. mastectomy); however, younger women were 4.2 times more likely to have breast reconstruction after mastectomy (95% confidence interval [CI], 2.4 –7.3; P ⬍0.0001). Younger women were more likely to receive chemotherapy (82.2% vs. 49.1%, P ⬍0.0001), particularly for earlier stage disease (stage I 63.2% vs. 29.7%, P ⬍0.0001; stage II 93.6% vs. 79.3%, P ⬍0.001). In women with node-negative tumors less than 1 cm in maximal diameter, 37% of the young women received chemotherapy versus 13% of older women (P ⫽ 0.01). There was no difference in the duration of chemotherapy between age groups, although duration of chemotherapy increased with increasing stage of disease in both groups. More women ⬎40 years of age were treated with hormonal therapy (71% vs. 57%, P ⫽ 0.0002), reflecting the higher likelihood of ER/PR-positive status in the older women. The overall recurrence rate in younger women was statistically higher than in older women (17.5% vs. 7%, P ⫽ 0.0002). Controlling for stage and type of initial surgery, the odds of recurrence were 2.2 times higher for patients under 40 than for those over 40 (95% CI, 1.3–3.7; P ⫽ 0.0025). These data are summarized in Table 2. In summary, our data demonstrate that the presentation
Overall recurrence Locoregional BCS Mastectomy Distant BCS Mastectomy
Women ⱕ 40 n (%)
Women ⬎ 40 n (%)
P
24 (18) 5 (4) 2 (2.9) 3 (4.4) 19 (14) 8 (12) 11 (16)
90 (7) 29 (2) 20 (2.5) 9 (1.8) 48 (3.6) 22 (2.7) 26 (5)
⬍0.0001 NS NS NS 0.02 NS NS
BCS ⫽ breast-conserving surgery; NS ⫽ not significant.
of younger women with breast cancer differs from that of older women diagnosed with the disease. Women under 40 years of age are more likely to present with palpable masses and have a higher stage of disease at presentation. In addition, they are less likely to have ER/PR-positive tumors. DCIS was found to be less common in these younger women. Despite differences in initial presentation, the surgical management of the primary tumor was similar between the two groups. However, in our institution, younger women choosing mastectomy were 4.2 times more likely to have breast reconstruction than their older counterparts. Similar trends in the use of postmastectomy reconstruction have been reported nationally [3]. Medical management with adjuvant therapy differed between the groups, with younger women being more likely to be treated with chemotherapy and older women more likely to receive hormonal therapy. These differences in management likely reflect the differences in ER/PR status seen in the two groups. Interestingly, younger women were more likely to receive adjuvant chemotherapy even in the setting of small (⬍1 cm), node-negative tumors. Several issues require careful consideration in this setting, as concerns of fertility after chemotherapy and vulnerability due to psychological stress have been shown to have a greater impact in the younger population [4]. The current National Comprehensive Cancer Network (NCCN) guidelines do not include age as a factor in determining the appropriateness of adjuvant chemotherapy for breast cancer [5]. However, this issue is somewhat controversial. Population-based data suggest that adjuvant chemotherapy may be warranted in younger women, even in the setting of low-risk disease. In a study by Kroman et al, younger women with low-risk disease had a higher mortality rate when adjuvant chemotherapy was not administered [6]. Our data support the findings of previous studies demonstrating a poorer prognosis in younger women with breast cancer. In our institution, younger women were more likely to develop recurrence, regardless of primary surgical treatment modality employed. This is in contrast to previously published reports, in which only younger women treated with breast conservation, not those treated with mastectomy, were more likely to develop recurrent disease than
D.M. Agnese et al. / The American Journal of Surgery 188 (2004) 437– 439
older women [7,8]. Although our study did not directly address survival, the majority of recurrences in these young women were distant recurrences, which likely correlates well with overall survival. Women ⱕ40 years of age diagnosed with breast cancer present with a disease with different biologic behavior than women over 40. These differences in presentation (palpable lump) and stage of disease (fewer cases of DCIS, more cases of advanced disease) may reflect the low likelihood of the performance of screening mammography in this age group and a lower index of suspicion. Regardless of these differences in presentation, the recurrence rate is higher in younger women when controlling for stage of disease at presentation and surgery performed. The increased use of chemotherapy in these younger women was a concerning finding in this study, particularly since the current practice guidelines do not support the use of age as a factor in determining the appropriateness of adjuvant chemotherapy. Further investigation is warranted to determine why these differences in disease presentation, treatment, and outcome exist so that future therapies can be tailored to benefit this population.
439
References [1] Xiong Q, Valero V, Kau V, et al. Female patients with breast carcinoma age 30 years and younger have a poor prognosis: the MD Anderson Cancer Center experience. Cancer 2001;92:2523– 8. [2] Chan A, Pintilie M, Vallis K, et al. Breast cancer in women ⱕ 35 years: review of 1002 cases from a single institution. Ann Oncol 2000;11:1255– 62. [3] Morrow M, Scott SK, Menck HR, et al. Factors influencing the use of breast reconstruction postmastectomy: a National Cancer Database study. J Am Coll Surg 2001;192:1– 8. [4] Shannon C, Smith IE. Breast cancer in adolescents and young women. Eur J Cancer 2003;39:2632– 42. [5] Carlson RW, Anderson BO, Edge SB, et al. The NCCN Breast Cancer Clinical Practice Guidelines in Oncology, version 3.2003. Available at: http://www.nccn.org/physician_gls/index.html. Accessed March 24, 2004. [6] Kroman N, Jensen M, Wohlfahrt J, et al. Factors influencing the effect of age on prognosis in breast cancer: a population based study. BMJ 2000;320:474 –9. [7] Arriagada R, Le MG, Contesso G, et al. Predictive factors for local recurrence in 2006 patients with surgically resected small breast cancer. Ann Oncol 2002;13:1404 –13. [8] Voogd AC, Nielsen M, Petrese JL, et al. Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol 2001;19:1688 –97.
Scientific paper
Trends in breast cancer presentation and care according to age in a single institution Doreen M. Agnese, M.D.a,*, Fouza Yusuf, M.P.H.b, John L. Wilson, Ph.D.b, Charles L. Shapiro, M.D.c, Amy Lehman, M.A.S.d, William E. Burak, Jr., M.D.a a
Division of Surgical Oncology, Department of Surgery, The Ohio State University, N924 Doan Hall, 410 W. 10th Ave., Columbus, OH 43210, USA b Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA c Department of Outcomes Management, The Ohio State University, Columbus, OH, USA d Center for Biostatistics, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA Manuscript received May 19, 2004; revised manuscript June 6, 2004 Presented at the Fifth Annual Meeting of the American Society of Breast Surgeons, March 31–April 4, 2004, Las Vegas, Nevada
Abstract Background: This study sought to determine the differences in presentation and treatment of young women (ⱕ40 years of age) with breast cancer. Methods: A prospective database was analyzed for differences in presentation and care in breast cancer patients ⱕ40 and ⬎40 years of age. Results: The study group consisted of 1685 women. Younger women were more likely to present with a palpable mass, have estrogen receptor/progesterone receptor (ER/PR)-negative tumors, and have more advanced disease at presentation. Although there was no difference in breast conservation rates, younger women were more likely to have postmastectomy reconstruction. Younger women were more likely to receive chemotherapy, even with node-negative tumors less than 1 cm in diameter (37% vs. 13%, P ⫽ 0.01). Conclusions: The presentation of younger women with breast cancer differs from that of older women. Although the surgical management is similar, adjuvant therapy differs, with younger women more likely to be treated with chemotherapy. © 2004 Excerpta Medica, Inc. All rights reserved. Keywords: Breast cancer; Young; Presentation; Therapy; Age
Breast cancer in young women is generally considered a more aggressive disease than that seen in older women. Numerous analyses have demonstrated a poorer prognosis in young women, even after controlling for stage at presentation [1,2]. The objective of this study was to determine the differences in presentation and treatment of young women (ⱕ40 years of age) with breast cancer. A prospective breast cancer database was established at the The Ohio State University in March 1998. All women diagnosed with breast cancer and receiving any portion of their treatment at The Ohio State University are entered into the database. This database was reviewed to identify all women diagnosed with breast cancer between March 1998 * Corresponding author. Tel.: ⫹1-614-293-6408; fax: ⫹1-614-2933465. E-mail address: [email protected]
and December 2002. The women with breast cancer identified during this interval were divided into two groups: those diagnosed at age ⱕ40 years, and those diagnosed at age ⬎40 years. Differences in presentation and treatment were sought. The variables analyzed included the mode of presentation, primary tumor characteristics, stage at diagnosis, and hormone receptor status. The primary operation, reconstructive surgery performed, and adjuvant therapy administered, including the type (chemotherapy or hormonal therapy) and duration of therapy, were also reviewed. Data relative to recurrence (local, regional, or distant) were also analyzed. Statistical analyses were performed using chisquare tests and logistic regression. Between March 1998 and December 2002, 1685 women were treated for breast cancer (ductal carcinoma-in-situ [DCIS] and invasive carcinoma) at The Ohio State University. One hundred sixty-three women were ⱕ40 and 1522
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved. doi:10.1016/j.amjsurg.2004.06.029
438
D.M. Agnese et al. / The American Journal of Surgery 188 (2004) 437– 439
Table 1 Differences in presentation and care of breast cancer in women ⱕ40 years of age Women ⱕ 40 n (%) Presentation with palpable mass DCIS Advanced stage (II, III, and IV) ER/PR positive Reconstruction after mastectomy Chemotherapy Chemotherapy for tumur ⬍1 cm (node negative) Hormonal therapy
Women ⬎ 40 n (%)
Table 2 Differences in recurrence after primary treatment for breast cancer in women ⱕ40
P
114 (70)
638 (42)
⬍0.0001
9 (6) 95 (67)
212 (16) 615 (45)
0.003 ⬍0.0001
88 (54) 48 (60)
971 (64) 193 (32)
0.02 ⬍0.0001
134 (82) 7 (37)
747 (49) 32 (13)
⬍0.0001 0.01
93 (57)
1088 (71)
0.0002
DCIS ⫽ ductal carcinoma-in-situ; ER/PR ⫽ estrogen receptor/progesterone receptor.
were ⬎40 years of age at the time of diagnosis. The results of this analysis are summarized in Table 1. Younger women were significantly more likely to present with a palpable mass (70% vs. 42%, P ⬍0.0001), and were more likely to have more advanced stage disease (II, III, and IV) at presentation (P ⬍0.0001). DCIS was seen less frequently in the younger population (P ⫽ 0.003). Fifty-four percent of the women ⱕ40 had estrogen receptor/progesterone receptor (ER/PR)-positive tumors compared with 64% of the women ⬎40 (P ⫽ 0.017). There was no difference in the rate of nodal positivity by size of the primary tumor between the groups. After controlling for stage of disease, there was no difference in the initial surgery performed (breast conservation vs. mastectomy); however, younger women were 4.2 times more likely to have breast reconstruction after mastectomy (95% confidence interval [CI], 2.4 –7.3; P ⬍0.0001). Younger women were more likely to receive chemotherapy (82.2% vs. 49.1%, P ⬍0.0001), particularly for earlier stage disease (stage I 63.2% vs. 29.7%, P ⬍0.0001; stage II 93.6% vs. 79.3%, P ⬍0.001). In women with node-negative tumors less than 1 cm in maximal diameter, 37% of the young women received chemotherapy versus 13% of older women (P ⫽ 0.01). There was no difference in the duration of chemotherapy between age groups, although duration of chemotherapy increased with increasing stage of disease in both groups. More women ⬎40 years of age were treated with hormonal therapy (71% vs. 57%, P ⫽ 0.0002), reflecting the higher likelihood of ER/PR-positive status in the older women. The overall recurrence rate in younger women was statistically higher than in older women (17.5% vs. 7%, P ⫽ 0.0002). Controlling for stage and type of initial surgery, the odds of recurrence were 2.2 times higher for patients under 40 than for those over 40 (95% CI, 1.3–3.7; P ⫽ 0.0025). These data are summarized in Table 2. In summary, our data demonstrate that the presentation
Overall recurrence Locoregional BCS Mastectomy Distant BCS Mastectomy
Women ⱕ 40 n (%)
Women ⬎ 40 n (%)
P
24 (18) 5 (4) 2 (2.9) 3 (4.4) 19 (14) 8 (12) 11 (16)
90 (7) 29 (2) 20 (2.5) 9 (1.8) 48 (3.6) 22 (2.7) 26 (5)
⬍0.0001 NS NS NS 0.02 NS NS
BCS ⫽ breast-conserving surgery; NS ⫽ not significant.
of younger women with breast cancer differs from that of older women diagnosed with the disease. Women under 40 years of age are more likely to present with palpable masses and have a higher stage of disease at presentation. In addition, they are less likely to have ER/PR-positive tumors. DCIS was found to be less common in these younger women. Despite differences in initial presentation, the surgical management of the primary tumor was similar between the two groups. However, in our institution, younger women choosing mastectomy were 4.2 times more likely to have breast reconstruction than their older counterparts. Similar trends in the use of postmastectomy reconstruction have been reported nationally [3]. Medical management with adjuvant therapy differed between the groups, with younger women being more likely to be treated with chemotherapy and older women more likely to receive hormonal therapy. These differences in management likely reflect the differences in ER/PR status seen in the two groups. Interestingly, younger women were more likely to receive adjuvant chemotherapy even in the setting of small (⬍1 cm), node-negative tumors. Several issues require careful consideration in this setting, as concerns of fertility after chemotherapy and vulnerability due to psychological stress have been shown to have a greater impact in the younger population [4]. The current National Comprehensive Cancer Network (NCCN) guidelines do not include age as a factor in determining the appropriateness of adjuvant chemotherapy for breast cancer [5]. However, this issue is somewhat controversial. Population-based data suggest that adjuvant chemotherapy may be warranted in younger women, even in the setting of low-risk disease. In a study by Kroman et al, younger women with low-risk disease had a higher mortality rate when adjuvant chemotherapy was not administered [6]. Our data support the findings of previous studies demonstrating a poorer prognosis in younger women with breast cancer. In our institution, younger women were more likely to develop recurrence, regardless of primary surgical treatment modality employed. This is in contrast to previously published reports, in which only younger women treated with breast conservation, not those treated with mastectomy, were more likely to develop recurrent disease than
D.M. Agnese et al. / The American Journal of Surgery 188 (2004) 437– 439
older women [7,8]. Although our study did not directly address survival, the majority of recurrences in these young women were distant recurrences, which likely correlates well with overall survival. Women ⱕ40 years of age diagnosed with breast cancer present with a disease with different biologic behavior than women over 40. These differences in presentation (palpable lump) and stage of disease (fewer cases of DCIS, more cases of advanced disease) may reflect the low likelihood of the performance of screening mammography in this age group and a lower index of suspicion. Regardless of these differences in presentation, the recurrence rate is higher in younger women when controlling for stage of disease at presentation and surgery performed. The increased use of chemotherapy in these younger women was a concerning finding in this study, particularly since the current practice guidelines do not support the use of age as a factor in determining the appropriateness of adjuvant chemotherapy. Further investigation is warranted to determine why these differences in disease presentation, treatment, and outcome exist so that future therapies can be tailored to benefit this population.
439
References [1] Xiong Q, Valero V, Kau V, et al. Female patients with breast carcinoma age 30 years and younger have a poor prognosis: the MD Anderson Cancer Center experience. Cancer 2001;92:2523– 8. [2] Chan A, Pintilie M, Vallis K, et al. Breast cancer in women ⱕ 35 years: review of 1002 cases from a single institution. Ann Oncol 2000;11:1255– 62. [3] Morrow M, Scott SK, Menck HR, et al. Factors influencing the use of breast reconstruction postmastectomy: a National Cancer Database study. J Am Coll Surg 2001;192:1– 8. [4] Shannon C, Smith IE. Breast cancer in adolescents and young women. Eur J Cancer 2003;39:2632– 42. [5] Carlson RW, Anderson BO, Edge SB, et al. The NCCN Breast Cancer Clinical Practice Guidelines in Oncology, version 3.2003. Available at: http://www.nccn.org/physician_gls/index.html. Accessed March 24, 2004. [6] Kroman N, Jensen M, Wohlfahrt J, et al. Factors influencing the effect of age on prognosis in breast cancer: a population based study. BMJ 2000;320:474 –9. [7] Arriagada R, Le MG, Contesso G, et al. Predictive factors for local recurrence in 2006 patients with surgically resected small breast cancer. Ann Oncol 2002;13:1404 –13. [8] Voogd AC, Nielsen M, Petrese JL, et al. Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol 2001;19:1688 –97.