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Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WIAlvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri.
Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WIMedical College of Wisconsin Cancer Center, Milwaukee, WI
Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WIMedical College of Wisconsin Cancer Center, Milwaukee, WI
Despite an aging population, there are no established treatment guidelines for women with ductal carcinoma in situ (DCIS) age ≥80. Here we describe national treatment patterns and survival outcomes in older women with DCIS.
Patients and Methods
Women age ≥80 diagnosed with DCIS from 2005 to 2014 were identified using the National Cancer Database. χ2, Fisher's exact test, and logistic regression models were used to identify factors influencing receipt of breast surgery, and Kaplan-Meier method and Cox proportional hazard models were used to evaluate overall survival (OS).
Results
A total of 6,070 women with DCIS met inclusion criteria, of which the majority (98%) received surgery. Receipt of surgery was independently associated with age <90. OS was higher for those who received surgery compared to those who did not (HR 2.2 [1.72-2.83] P < .001).
Conclusion
The vast majority of patients age ≥80 with DCIS in the National Cancer Database received primary surgical management, which was associated with a significant OS benefit. Considering comorbidities and patient fitness, surgical resection should be considered for all patients age ≥80 who are suitable operative candidates.
Ductal carcinoma in situ (DCIS) is non-invasive, stage 0 breast cancer, where proliferation of malignant cells is limited to the ducts of the breast tissue.
The optimal management of DCIS is frequently studied and debated and ongoing clinical trials are currently examining if omission of surgery may be suitable in select patients.
The COMET (comparison of operative versus monitoring and endocrine therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS).
It is often questioned whether patients with DCIS should undergo treatment in accordance with guidelines, or whether some patients may forgo parts of treatment without an impact on mortality.
The COMET (comparison of operative versus monitoring and endocrine therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS).
These concerns are especially relevant for the older population, who, due to differences in life expectancy, competing comorbidities, and lifestyle values, may benefit from de-escalation in therapy.
In a previous study of invasive cancer in women age ≥80, we found the majority of patients underwent surgery and this finding came with a significant overall survival (OS) advantage. Our findings highlighted that providing surgery should not be based on age alone.
As DCIS management is associated with more controversy, an investigation of treatment patterns in women age ≥80 is especially relevant. Thus, we used the National Cancer Database (NCDB) to identify women age ≥80 with DCIS to describe treatment patterns and examine OS to assess whether a survival advantage exists for patients who underwent surgical resection.
Methods
The NCDB was used to identify women age ≥80 with a diagnosis of DCIS from 2005-2014. The NCDB is a nation-wide, facility-based, comprehensive clinical oncology data set and captures approximately 70% of all newly diagnosed malignancies in the US annually.
NCDB data is de-identified and this investigation was deemed exempt by our Institutional Review Board.
To ensure patients included in this analysis were diagnosed with DCIS pathology, patients whose International Classification of Disease for Oncology (ICD-O) histology codes that did not match DCIS histology were excluded, including women with Paget's disease without underlying DCIS. Women with invasive breast cancer histology or evidence of metastatic disease including clinical or pathologic stage M1, and those who received radiation directed outside of the breast, chest wall, or regional lymph nodes were excluded from analysis. The cohort was limited to women for whom breast cancer was their only documented malignancy and included only patients who received most or all of their treatment at the reporting facility (Figure 1).
Figure 1Flow chart of cohort inclusion and exclusion criteria for evaluation of women age ≥80 with DCIS in the National Cancer Database.
Analysis included collection of demographic information including race/ethnicity, age, Charlson-Deyo comorbidity score, and care facility type. Cancer characteristics examined included tumor grade and estrogen receptor (ER) and progesterone receptor (PR) status. Treatment variables included type of breast surgery and receipt of radiation therapy and/or endocrine therapy. χ2 test, Fisher's exact test, and logistic regression models were used to identify factors influencing receipt of surgery. Kaplan-Meier method and Cox proportional hazards models were used to evaluate OS.
Results
The final cohort consisted of 6,070 patients (Figure 1 and Table 1). The majority of patients were White (79%), age 80 to 89 at diagnosis (95%), and were healthy (96%) as defined by a Charlson-Deyo score of 0 or 1. Almost all patients had breast surgery (98%), of which 78% underwent lumpectomy. While median follow-up was 55 months for those who had surgery, it was only 44 months for those who did not receive surgery (Table 1). On univariate analysis, White patients (P = .003), those age <85 (P < .001), and those with higher grade tumors (P = .003) were more likely to receive surgery. The most common reason for not receiving surgery was patient refusal (63% of those who provided reasoning). Only 40% of patients who underwent lumpectomy also received radiation. The most cited reason for omission of radiation was patient refusal (72% of those who provided reasoning). Seventy percent (n = 4267) of patients had hormone-receptor positive disease. Of those with hormone receptor-positive disease, only 62% (n = 27,128) received endocrine therapy. Additionally, 26% (n = 11,329) of patients with hormone receptor-positive DCIS received both endocrine therapy and radiation therapy. When compared with academic programs, surgical management of DCIS was more likely to be performed in community and comprehensive community cancer programs (P = .04, Table 1).
Table 1Characteristics of Women Age ≥80 With DCIS by Receipt of Surgery.
Abbreviations: ARP = academic/research program; CCP = community cancer program; CCCP = comprehensive community cancer program; INCP = integrated network cancer program, NH=non-Hispanic.
CCP CCCP ARP INCP
707 (11.6) 3212 (52.9) 1449 (23.9) 702 (11.6)
695 (11.7) 3151 (53.0) 1405 (23.6) 691 (11.6)
12 (9.4) 61 (47.7) 44 (34.4) 11 (8.6)
.041
a Reported percentages are percent of total available answers in scarcely reported variables
b Abbreviations: ARP = academic/research program; CCP = community cancer program; CCCP = comprehensive community cancer program; INCP = integrated network cancer program, NH=non-Hispanic.
On multivariate analysis, those age <90 were more likely to undergo surgery as well as those with higher grade tumors (P < .05, Table 2). Black women were half as likely to receive surgery vs. White women (P = .01), and women who received care at an academic research program were less likely to undergo surgery (P = .04, Table 2).
Table 2Multivariate Analysis of Factors That are Associated With Receipt of Surgery in Women Age ≥80 With DCIS.
Abbreviations: ARP = academic/research program; CCP = community cancer program; CCCP = comprehensive community cancer program; INCP = integrated network cancer program.
INCP ARP CCP CCCP
1 (Ref) 0.44 0.69 0.74
0.20-0.96 0.27-1.76 0.34-1.59
.04 .441 .437
Grade III II I
1 (Ref) 0.59 0.40
0.36-0.97 0.23-0.69
.039 <.001
a Abbreviations: ARP = academic/research program; CCP = community cancer program; CCCP = comprehensive community cancer program; INCP = integrated network cancer program.
Multivariate analysis of factors associated with mortality demonstrated surgery was an independent predictor of OS (P < .001; HR 0.46, 95% CI: [0.34-0.63]). Increasing age was associated with decreased OS as was the presence of increasing number of comorbidities (Table 3). In addition, those who received radiation had improved OS (P < .001, HR 0.67, 95% CI: [0.59-0.76], Table 3). On Kaplan-Meier analysis, OS was higher for women who received surgery compared to those who did not (P < .001) with a hazard ratio of 2.2 (95% CI: [1.72-2.83], Figure 2).
Table 3Multivariate Analysis of Factors That are Associated With Mortality in Women Age ≥80 With DCIS.
Treatment patterns and outcomes for DCIS in older women is an area that is not well-studied. Here, we describe these patterns for women age ≥80 diagnosed with DCIS over a 10-year period using the NCDB.
In this cohort, the vast majority (98%) underwent primary surgical management, which was associated with a significant OS benefit. While some studies have demonstrated that older women are less likely than younger patients to undergo breast cancer surgery,
The relationship between patient and tumor characteristics, patterns of breast cancer care, and 5-year survival among elderly women with incident breast cancer.
. In this analysis, lumpectomy was performed more often than mastectomy (78% and 22%, respectively). This finding is in concordance with other studies, although this study specifically describes this trend in older women with DCIS and is expected given the lower morbidity of lumpectomy.
Despite these results, the question of appropriate candidacy for surgery in older patients with DCIS remains. This data demonstrates a survival benefit, and the decision to offer surgery should not be based on age alone. While it has been shown that omission of certain therapies in some situations does not negatively affect survival, such as the omission of axillary staging in older women with node-negative early-stage invasive breast cancer who are candidates for endocrine therapy,
questions remain in elucidating which patients are ideal operative candidates. Active surveillance has been shown to be an appropriate management strategy for patients with multiple competing comorbidities
The COMET (comparison of operative versus monitoring and endocrine therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS).
Our study demonstrates those with lower grade DCIS were less likely to undergo surgery, consistent with physician comfort with active surveillance as low grade disease is unlikely to impact mortality. There are ongoing investigations to examine if there may be certain forms of DCIS in which surgery can omitted. The Alliance COMET (Comparison of Operative to Monitoring and Endocrine Therapy) trial is currently investigating whether surgery for low-risk, hormone-receptor positive DCIS is warranted.
The COMET (comparison of operative versus monitoring and endocrine therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS).
This clinical question is particularly relevant to the older population as surgery may possibly be omitted in many older patients, especially those who are suboptimal surgical candidates.
Conversely, prevention of disease progression, even in older patients, may be beneficial in those with otherwise high projected survival (ie, no competing comorbidities and high functional status). Our data show no difference in survival based on ER status and worsened survival with PR negative disease, however surgical management of DCIS remains the only option for whom endocrine therapy is not a possibility (ie, hormone receptor-negative or contraindication to endocrine therapy). In addition, it should also be considered for those with high grade disease,
and in those who are otherwise good candidates for surgery. It has been shown that survival correlates more strongly with extent of surgical therapy compared with patient age, indicating that factors outside of age are greater drivers of outcomes.
Comorbid conditions are prevalent in the older population and taking time for medical optimization may be of benefit prior to surgery since relatively brief delays in DCIS treatment does not affect survival or disease progression.
In our study, the median follow-up was 55 months for those who received surgery and 45 months for those who did not, representing an almost 1-year increase in follow-up and survival benefit in those who had surgery. The shorter follow-up duration in the non-surgical group may indicate a selection bias with inclusion of patients who were deemed unfit for surgery and died prior to receiving treatment. It has been shown that the majority of morbidity in older patients with DCIS is due to causes other than breast cancer,
confirming the need to identify all health factors which may contribute to a patient's candidacy for surgery. In our study, comorbidity was assessed using Charlson-Deyo scores, which does not encompass the entire health status of a patient, and does not include frailty, which is a highly important factor in the multidisciplinary oncological decision-making process for older patients. Guideline-concordant treatment including surgery and/or radiation therapy can pose a potentially significant morbidity burden which may be more severe in patients with underlying comorbid conditions.
The use of adjuvant radiation therapy for DCIS in older women is also controversial. We found radiation therapy was used in 40% of lumpectomy patients, which is similar to rates described in other older cohorts but lower than rates seen in younger women.
Radiation therapy did confer a survival advantage in this cohort. A SEER-Medicare review of patients age ≥65 found that patients with ER-positive DCIS do receive endocrine therapy more often when they undergo lumpectomy with radiation therapy,
indicating a preference to follow guideline-concordant therapy for patients who undergo surgery. A similar SEER-Medicare analysis of DCIS patients demonstrated receipt of lumpectomy as well as radiation therapy was shown to decrease breast cancer-specific mortality compared with those who received lumpectomy alone.
This finding may support receipt of full guideline-concordant treatment in healthy patients with high-risk DCIS.
In patients with invasive breast cancer, the CALGB 9343 study revealed no change in mortality with omission of radiation therapy in patients age ≥70 with early stage, clinically-node negative, hormone receptor-positive invasive breast cancer who underwent lumpectomy followed by endocrine therapy.
Omission of therapies in older patients with DCIS is best implemented in those with low risk disease and significant competing comorbidities who are unlikely to die of DCIS. However, identifying patients with low-risk DCIS in which de-escalation of therapy may be warranted, remains to be entirely understood,
and weighing comorbidities in comparison with cancer treatment can be difficult. The International Society of Geriatric Oncology and European Society of Breast Cancer Specialists, acknowledge no proven survival advantage for patients ≥70 with DCIS who receive radiation therapy and recommend full consideration of an individual's comorbidities and the potential harms of radiation.
Management of eldelry patients with breast cancer: updated recommendations of the internal society of geriatric oncology (SIOG) and European society of breast cancer specialists (EUSOMA).
Shared decision-making and full understanding of patient functional status are both important elements of care in older patients, and there have been tools established which have demonstrated effectiveness in these areas.
Older breast cancer survivors: geriatric assessment domains are associated with poor tolerance of treatment adverse effects and predict mortality over 7 years of follow-up.
The limitations of this study are largely due to the retrospective nature of the data with dependence on accuracy of data input from multiple sources. Additionally, our analysis was based on outcomes and survival data, but the NCDB does not report disease-specific survival. Given the indolent nature of breast cancers in older patients and the more limited life expectancy of this population compared to younger women, older patients are more likely to die of competing comorbidities,
The relationship between patient and tumor characteristics, patterns of breast cancer care, and 5-year survival among elderly women with incident breast cancer.
making cancer-specific survival likely less important here compared with a study of younger patients. Additionally functional status of patients is not available in the NCDB, however it is important to identify vulnerabilities in patients prior to planning treatment
that may affect quality of life for individual patients, and it must be presumed that this was taken into account when planning treatments for these older patients. Future prospective studies of DCIS in older patients will continue to identify candidates for omission of therapies to preserve quality of life without influencing survival, further delineate optimal treatment patterns specific to older women, and recognize pathologic elements unique to DCIS and how they may impact treatment options.
Conclusion
Here, we describe treatment patterns and survival outcomes in women age ≥80 with DCIS using the NCDB. Almost all patients received surgery, of which the majority underwent lumpectomy, and those who underwent surgery had an improved OS compared to those who did not. Therefore, surgical intervention should be considered in patients who are appropriate surgical candidates despite increased age. The inclusion of treatment options for older women with DCIS should be a careful balance of risks and benefits, comprehensive health and functionality assessment, and discussion of goals with patients, their families, and the multidisciplinary breast cancer treatment team. Continued evaluation of treatment patterns, in conjunction with improved understanding of DCIS pathology and its impact on older patients, is necessary for complete understanding of treatment of this disease in this population.
Clinical Practice Points
•
Determining the optimal clinical care of DCIS is ongoing. Given the paucity of data on national treatment patterns and survival outcomes in older breast cancer patients, there is a need for a greater understanding of the management and outcomes of older women with DCIS.
•
Using the National Cancer Database, we describe an overall survival benefit to receipt of surgery in patients with DCIS who are age ≥80. This study identifies an overall healthy cohort of women ≥80 with DCIS, with increased utilization of surgical treatment in those who are younger and with fewer comorbidities.
•
Given the independent survival advantage to receiving surgery ± radiation therapy, emphasis should be placed on the importance of considering interventions in a shared decision-making manner and not based on age alone.
References
Meijnen P
Oldenburg HSA
Peterse JL
Bartlelink H
Rutgers EJT.
Clinical outcome after selective treatment of patients diagnosed with ductal carcinoma in situ of the breast.
The COMET (comparison of operative versus monitoring and endocrine therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS).
The relationship between patient and tumor characteristics, patterns of breast cancer care, and 5-year survival among elderly women with incident breast cancer.
Management of eldelry patients with breast cancer: updated recommendations of the internal society of geriatric oncology (SIOG) and European society of breast cancer specialists (EUSOMA).
Older breast cancer survivors: geriatric assessment domains are associated with poor tolerance of treatment adverse effects and predict mortality over 7 years of follow-up.
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