Abstract
Purpose of Review
Over the past decade, prospective clinical trials and retrospective data have changed clinical guidelines for the treatment of older patients, most notably those patients with early, hormone receptor-positive, clinically node-negative breast cancer. Here is a comprehensive review of the literature supporting de-escalation of local-regional therapy in older patients with breast cancer.
Recent Findings
The de-escalation of treatment in elderly patients includes minimizing surgical interventions and adjuvant radiation therapy. Current Choosing Wisely® guidelines recommend considering the omission of surgical staging of the axilla in patients ≥ 70 with early-stage, hormone receptor-positive breast cancer. Primary endocrine therapy may be a suitable option for older patients with hormone receptor-positive breast cancer and short life-expectancy. The long-term results of the CALGB 9343 clinical trial reveal that radiotherapy omission is not associated with a survival benefit in patients ≥ 70 with early-stage, hormone receptor-positive, node-negative breast cancer, who receive 5 years of adjuvant endocrine therapy. The results of the RAPID trial support that shorter courses of radiation therapy are non-inferior to standard therapy and may be of significant value to older patients who require radiation. In addition, intraoperative radiotherapy may be useful in older patients with mobility issues who have higher-risk tumors and the current TARGIT-E aims to assess IORT in patients ≥ 70 with hormone receptor-positive tumors.
Summary
Select older patients with breast cancer may benefit from the omission of axillary staging, less aggressive breast surgery, and shorter courses or total omission of radiation therapy. Current studies aim to continue to define the appropriate criteria for which older patients can benefit from de-escalation of local-regional therapy.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
The annual number of new cases of breast cancer is steadily increasing in women age 70 and older. Compared to all other age groups, women in their eighth decade of life have the highest age-specific incidence of breast cancer [1]. Currently, approximately 30% of new annual breast cancer cases in the USA are in women over the age of 70, and this percentage is anticipated to increase to 34% by 2030 [1, 2]. This patient population has unique intrinsic biological and social characteristics compared to their younger cohorts, such as higher rates of comorbid conditions, less social support, and transportation barriers.
Over the past two decades, clinical trials have aimed to optimize the risk-benefit ratio for treatment options for older patients with breast cancer including incorporating less invasive breast and axillary lymph node surgery, abbreviated radiation therapy regimens, and, in some instances, possible omission of radiation therapy and surgery. Through the national media, the general public has also become aware of the de-escalation of cancer care in older adults and has further emphasized the need to assess treatment benefits and risks [3]. In certain circumstances, the primary objective of omitting therapy is to optimize patient treatment while simultaneously minimizing adverse side-effects and unnecessary healthcare costs. This review aims to summarize the published literature that supports de-escalation of surgery and radiation in older women with breast cancer.
Surgical Therapy
Repeat Segmental Mastectomy for Recurrence
Standard therapy for a breast cancer recurrence in a patient who has previously received breast conservation therapy (BCT) is completion mastectomy [4]. However, repeat segmental mastectomy (with or without radiation therapy) may be an appropriate treatment regimen for select older patients [5••]. Consideration for this treatment option is partially due to the increase in post-operative disability seen in elderly patients who undergo mastectomy compared to those who undergo BCT [6]. A single-institution retrospective analysis found that while increasing patient age was associated with a decrease in the conformation of NCCN guidelines, there was no difference in local-regional recurrence, development of distant-disease, or breast cancer-related death [7]. Repeat segmental mastectomy can be considered for those patients with early-stage hormone receptor-positive tumors, who are also appropriately selected patients for radiotherapy omission based on clinical trial evidence [8•, 9••, 10••].
Axillary Nodal Staging
The role of axillary staging with sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) in older breast cancer patients has been a topic of consideration in recent years. Both procedures incur a risk of lymphedema development, which can be especially debilitating in older patients, although the risk of lymphedema development has been shown to be independent of chronological age [11]. In the setting of a clinically negative axilla, the role of nodal staging should be discussed in collaboration with the patient and the multidisciplinary breast cancer team to determine how nodal staging may influence adjuvant systemic and radiation therapy. If therapy will not be dictated by pathologically positive nodal disease, an omission of SLNB should be considered [12••]. Additionally, predictive models exist to aid in determining the likelihood of axillary nodal positivity and can also be incorporated into the decision-making process for the role of SLNB in the older patient with breast cancer [13•, 14].
In 2016, the Society of Surgical Oncology along with American Board of Internal Medicine released the Choosing Wisely® guidelines which recommend clinicians to consider omitting routine SLNB in women age ≥ 70 with early-stage, hormone receptor-positive, Her2-negative breast cancer with a clinically negative axilla [15•]. This guideline was largely supported by clinical trial evidence demonstrating no significant difference in breast cancer mortality in older patients with clinically T1 N0 hormone receptor-positive disease who received tamoxifen, when randomized to undergo ALND or no ALND [16•]. Since the release of these guidelines, several studies have demonstrated a steady decline in the rate of SLNB in older patients over the past several years [17, 18••].
Patient selection for the omission of axillary staging plays a critical role in optimizing care in the elderly as there is some data to support that nodal staging may improve survival [19•, 20•]. A retrospective study of the National Cancer Database (NCDB) analyzed over 133,000 women age ≥ 70 with clinical T1-T3 tumors, node-negative breast cancers who were then subdivided by those who underwent nodal staging versus those who did not. The authors found that patients who underwent nodal staging were more likely to receive adjuvant systemic and radiation therapy and had a higher rate of overall-survival; however, this finding may be attributable to patient selection bias of those who underwent nodal staging [19•]. Similarly, an analysis of the Surveillance, Epidemiology, and End Results Program (SEER) database found that in older women with stage 1 disease, increasing age was associated with a decrease in the rate of SLNB and, when controlling for other factors, may actually have a negative impact on outcome [20•]. The most recent NCCN guidelines highlight the lack of definitive findings to definitively conclude improved survival with nodal staging in elderly patients or to formally recommend nodal staging for those patients when its findings are unlikely to alter adjuvant therapies [4].
Complete Surgical Omission
Perhaps the most controversial topic for surgical de-escalation in older patients is the total omission of surgery for operable breast cancer. Surgical omission has seen an increase over the past decade, especially in those patients age ≥ 80, and may be warranted in select patients, such as those who are more likely to succumb due to their comorbidities rather than their breast cancer [21]. Online tools such as the University of California San Francisco’s ePrognosis are available to the public and provide patient estimated life expectancy based on comorbidities and have previously been validated for patients with early-stage breast cancer [22, 23]. Additional tools such as the comprehensive geriatric assessment (CGA) can also be used. The CGA incorporates an individual’s functional and cognitive status, nutritional state, psychological well-being social support, and medical conditions to predict morbidity and mortality in older oncology patients [24]. Primary endocrine therapy may be an option for patients with hormone receptor-positive breast cancer who are unsuitable surgical candidates given their other health conditions or for those patients who refuse surgery [25, 26]. A previous Cochrane meta-nalysis demonstrated that there was an improved progression-free survival for those patients with hormone receptor-positive tumors who underwent surgery; however, additional clinical trials have not demonstrated a direct impact on improvement in survival [26, 27, 28••].
Radiation Therapy
Adjuvant radiation therapy (RT) is generally well-tolerated by most older women, with evidence showing a decrease in local-regional recurrence rates and improved survival [29•]. However, as with surgical decision-making, several factors influence the role of RT in elderly patients. These include, but are not limited to, patient frailty, overall prognosis, patient mobility and physical limitations, time and transportation constraints, and adverse side effects of RT [30, 31]. Short-term follow-up analysis has revealed that overall quality of life in older patients who receive RT is largely unchanged compared to those who do receive RT [32•]. Additionally, those patients who are most likely to benefit from de-escalation of adjuvant RT are those with early-stage, hormone receptor-positive, clinically node-negative breast cancers who are suitable candidates for breast-conserving surgery and adjuvant endocrine therapy [33••].
Hypofractionated/Accelerated, Whole Breast Radiation Therapy (WBRT)
To minimize the timeframe needed to receive adjuvant RT, conventionally fractioned WBRT has largely been replaced by hypofractionated (also known as “accelerated”) WBRT for women with early-stage, node-negative breast cancer. Long-term results have demonstrated that a hypofractionated course of RT is non-inferior to conventional RT regimens and allows the conventional administration time of 5–7 weeks to be shortened to a 3–5-week course [34•]. This decrease in administration duration can aid in minimizing patient transportation issues that older breast cancer patients may face. Several prospective studies have demonstrated that hypofractionated WBRT in elderly breast cancer patients is non-inferior to conventional fractionation, well-tolerated by the majority of patients, and provides lower transportation and temporal constraints for patients [35,36,37, 38•, 39].
Accelerated Partial Breast Irradiation (APBI) and Intraoperative Radiotherapy (IORT)
Given the success of hypofractionated WBRT, radiotherapy administration protocols have been developed to assess the role of APBI after breast-conserving surgery. APBI further decreases the time needed for RT administration down to 1–2 weeks and spares radiation to healthy tissues. If the RT dose is targeted towards the lumpectomy site, then larger doses can be given over a shorter duration [40••]. APBI can be administered through either brachytherapy catheters or external beam RT. The current American Society for Therapeutic Radiation Oncology (ASTRO) guidelines dictate that outside of the clinical trial setting, only patients ≥ 50 years of age who undergo BCT with negative margins (defined as at least 2 mm) for DCIS or T1 lesions, with low to intermediate grade tumors, should currently be considered for APBI [40••]. Several clinical trials have demonstrated that although APBI is non-inferior compared to WBRT for local recurrence rates, long-term toxicity and adverse cosmesis do occur more frequently in those patients who undergo APBI [41••, 42]. APBI may be exceptionally warranted for those older patients who meet ASTRO guideline criteria and have challenging transportation and mobility issues, to allow the administration time frame to be substantially decreased.
Intraoperative radiotherapy (IORT) was designed to allow for a single dose of radiation to be given directly to the lumpectomy cavity during the patient’s initial operation. Two large clinical trials demonstrated that when comparting IORT to WBRT, there was an increase in the rate of local recurrence in the IORT group; however, for select patients, this recurrence rate was acceptable at less than 2% at 5 years [43, 44]. A recent analysis demonstrated that performing a delayed dose of a single IORT, by reopening the lumpectomy cavity, had similar overall survival to standard WBRT, but again demonstrated a higher local-regional recurrence rate [45]. Those older patients with favorable tumors who undergo lumpectomy and have contraindications to conventional adjuvant RT, may undergo IORT instead of conventional RT. Recent data reveals that patient health-related quality of life is similar between those who receive APBI in either the external beam or intraoperative settings in patients ≥ 60 years of age, but that acute local radiation side effects may be higher in those who receive IORT [46, 47]. A multi-institutional retrospective registry revealed that when comparing those patients age < 70 and ≥ 70 who receive IORT, acute toxicity and 1-year local recurrence rates were similar between the two age groups [48]. Currently, the TARGET-E study, a prospective phase 2 study of IORT in elderly patients, aims to further investigate the efficacy of a single RT dose in patients ≥ 70 years of age with small, node-negative breast cancers by evaluating local recurrence rates, survival, toxicity, and quality of life after 10 years [49••].
RT Omission
The most data-rich topic for de-escalation in local-regional RT in the elderly is in omitting RT for select patients with early-stage, node-negative, hormone receptor-positive tumors. In 2004, Hughes and colleagues first published the 5-year results of the Cancer and Leukemia Group B (CALGB) 9343 randomized controlled clinical trial. CALGB 9343 randomized 636 women age ≥ 70 with cT1-T2, N0, hormone receptor-positive tumors who underwent BCT to receive tamoxifen alone or tamoxifen plus conventional WBRT [8•]. While there was a higher incidence in local-regional recurrence in patients who received tamoxifen alone (4% vs 1%), there was no difference in the rates of mastectomy for recurrence, development of distant disease, or overall survival at 5 years [8•]. Subsequently, in 2013, long-term follow-up (mean of 12.6 years) demonstrated similar findings with a 10-year overall survival rate of 67% for the tamoxifen plus radiotherapy group versus 66% for the tamoxifen group alone (p < 0.05) [9••]. A similar study was performed during the same time period in Europe: the PRIME II clinical trial. PRIME II included women ≥ 65 with cT1-T2 (up to 3 cm), N0, hormone receptor-positive tumors who were undergoing BCT [10••]. Those patients with grade 3 tumors or those with lymphovascular invasion were included, but patients were not allowed to have both features. As in CALGB 9343, patients were randomized to receive endocrine therapy (ET) alone or RT and ET. Five-year survival rates were similar between the two groups, but they did observe a modest reduction in ipsilateral recurrence in those patients who received RT [10••]. These two clinical trials made a substantial impact on treatment guidelines and led to an overall decrease in the rates of RT and decrease in the rates of mastectomy in older patients with breast cancer [50,51,52]. However, adherence with adjuvant ET in the setting of RT omission remains a significant predictor in long-term outcomes and patient compliance with ET should be carefully followed over the subsequent years after initiating ET [53•, 54]. Detailed and supportive communication has demonstrated to be key factors for adherence within this patient demographic [55].
Additional studies have been performed to validate the findings of these two large clinical trials [55]. Two separate meta-analyses from 2017 pooled data from four randomized controlled trials and confirmed that while RT does reduce the risk of ipsilateral recurrence, it does not impact distant or overall survival in older patients with early-stage, hormone receptor-positive, node-negative breast cancer treated with BCT and ET alone [56, 57•]. More recent clinical trials have expanded inclusion criteria for RT omission to assess if the findings in women age ≥ 70 can be applied to additional age groups. A prospective randomized control trial in Tokyo included 203 women, age ≥ 60 with cT1-T2 (up to 3 cm), node-negative, hormone receptor-positive tumors without evidence of lymphovascular invasion, who underwent BCT and had a tumor-free margin of ≥ 5 mm and were randomized to receive ET alone or ET and WBRT [58]. The trial found no difference in ipsilateral recurrence or overall survival at 5 years. While some patients did receive systemic chemotherapy within this cohort, the authors found no difference between recurrence or overall survival when controlling for systemic chemotherapy between the two treatment arms [58].
In addition, RT omission may be considered in those patients with significant transportation issues, comorbidities that may alter the benefit of local-regional control with RT, or those with an absolute contraindication to RT, regardless of tumor stage or tumor biology [59]. While chronological age is associated with a lower likelihood of receiving RT, even in the setting of nodal involvement, RT omission should be guided by the multidisciplinary breast cancer team and overall assessment of the benefit of RT to the patient [60]. It should be noted that in older patients with hormone receptor-negative disease, it appears that radiotherapy does improve overall and disease-specific survival [61••, 62•, 63]. These findings highlight the significance of careful patient selection for RT omission and how treatment plans should be carefully evaluated and discussed by the multidisciplinary breast cancer treatment team.
Conclusion
Over the past two decades, substantial clinical evidence has arisen to demonstrate that de-escalation of local treatment for breast cancer can be safe and effective in select older patients. The older patient with breast cancer needs a carefully selected plan that is not only tailored to the patient’s specific needs but made by the multidisciplinary breast cancer team in collaboration with both patients and their family members. Careful attention must be made by providers to design treatment plans that utilize clinical data to maximize patient benefit while simultaneously minimize the risks of surgery and radiation therapy.
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Cancer Stats: United States Cancer Statistics. Centers for Disease Control and Prevention. https://gis.cdc.gov/Cancer/USCS/DataViz.html. Accessed 21 June 2020.
National Cancer Institute. Study Forecasts New Breast Cancer Cases by 2030. https://www.cancer.gov/news-events/cancer-currents-blog/2015/breast-forecast. Accessed 21 June 2020.
Span P. For elderly women with breast cancer, surgery may not be the best option. The New York Times, [online] 2018. https://www.nytimes.com/2018/09/14/health/breast-cancer-surgery-elderly.html. Accessed 21 June 2020.
NCCN Clinical Practice Guidelines in Oncology. Breast Cancer Version 4.2020. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed 21 June 2020.
•• NCCN Clinical Practice Guidelines in Oncology. Older Adult Oncology Version 1.2020. https://www.nccn.org/professionals/physician_gls/pdf/senior.pdf. Accessed 21 June 2020. National cancer guidelines with considerations for older adults with breast cancer.
Sada A, Day CN, Hoskin TL, Degnim AC, Habermann EB, Hieken TJ. Mastectomy and immediate breast reconstruction in the elderly: Trends and outcomes. Surgery. 2019;166(4):709–14. https://doi.org/10.1016/j.surg.2019.05.055.
Agborbesong O, Helmer SD, Reyes J, Strader LA, Tenofsky PL. Breast cancer treatment in the elderly: do treatment plans that do not conform to NCCN recommendations lead to worse outcomes? Am J Surg. 2020;220(2):381–4. https://doi.org/10.1016/j.amjsurg.2019.12.007.
• Hughes KS, Schnaper LA, Berry D, Cirrincione C, McCormick B, Shank B, et al. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004;351(10):971–7. https://doi.org/10.1056/NEJMoa040587. Initial results of the CALGB 9343 trial, demonstrating that in women age 70 with cT1-T2 N0 hormone-receptor positive tumors who undergo lumpectomy, radiation can be omitted if women receive 5 years of endocrine therapy with no difference in overall or distant disease-free survival.
•• Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, 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):2382–7. https://doi.org/10.1200/JCO.2012.45.2615Long-term results of the CALGB 9343 trial, demonstrating that in women age ≥70 with cT1-T2 N0 hormone-receptor positive tumors who undergo lumpectomy, radiation can be omitted if women receive 5 years of endocrine therapy with no difference in overall or distant disease-free survival.
•• Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM, PRIME II investigators. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial [published correction appears in Lancet Oncol. 2015 Mar;16(3):e105]. Lancet Oncol. 2015;16(3):266–73. https://doi.org/10.1016/S1470-2045(14)71221-5Randomized control trial that demonstrated that in women age ≥65 with T1-T2 (up to 3cm) N0, hormone-receptor positive tumors who receive endocrine therapy, ipsilateral recurrence is low enough to allow for omission of radiation in some patients.
Yen TW, Fan X, Sparapani R, Laud PW, Walker AP, Nattinger AB. A contemporary, population-based study of lymphedema risk factors in older women with breast cancer. Ann Surg Oncol. 2009;16(4):979–88. https://doi.org/10.1245/s10434-009-0347-2.
•• Liang S, Hallet J, Simpson JS, Tricco AC, Scheer AS. Omission of axillary staging in elderly patients with early stage breast cancer impacts regional control but not survival: a systematic review and meta-analysis. J Geriatr Oncol. 2017;8(2):140–7 Included two randomized control trials (using PRISMA guidelines) and found that omission of axillary staging in cN0 elderly patients had an increase in regional recurrence, but no difference on survival.
• Welsh JL, Hoskin TL, Day CN, Habermann EB, Goetz MP, Boughey JC. Predicting nodal positivity in women 70 years of age and older with hormone receptor-positive breast cancer to aid incorporation of a society of surgical oncology choosing wisely guideline into clinical practice. Ann Surg Oncol. 2017;24(10):2881–8. Utilizing the NCDB, the authors created a model that demonstrated that early stage, low grade tumors have a lower rate of nodal positive disease.
Greer LT, Rosman M, Charles Mylander W, Liang W, Buras RR, Chagpar AB, et al. A prediction model for the presence of axillary lymph node involvement in women with invasive breast cancer: a focus on older women. Breast J. 2014;20(2):147–53. https://doi.org/10.1111/tbj.12233.
• Choosing Wisely® Society of Surgical Oncology. Don’t routinely use sentinel node biopsy in clinically node negative women ≥70 years of age with early stage hormone receptor positive, HER2 negative invasive breast cancer. https://www.choosingwisely.org/clinician-lists/sso-sentinel-node-biopsy-in-node-negative-women-70-and-over/. Accessed 23 June 2020. Practice changing guideline on SLNB omission in older patients with early stage and favorable tumors.
• Martelli G, Boracchi P, Ardoino I, Lozza L, Bohm S, Vetrella G, et al. Axillary dissection versus no axillary dissection in older patients with T1N0 breast cancer: 15-year results of a randomized controlled trial. Ann Surg. 2012;256(6):920–4. https://doi.org/10.1097/SLA.0b013e31827660a8. Fifteen year follow-up of a randomized clinical trial in 238 older breast cancer patients with cT1 N0 disease that revealed no difference in rates of distant metastasis, overall survival, or breast-cancer specific survival between those that received an ALND vs those that did not.
Calderon E, Webb C, Kosiorek HE, Richard J, Gray MD, Cronin P, et al. Are we choosing wisely in elderly females with breast cancer? Am J Surg. 2019;218(6):1229–33. https://doi.org/10.1016/j.amjsurg.2019.08.004.
•• Christian N, Heelan Gladden A, Friedman C, Gleisner-Patton A, Murphy C, Kounalakis N, et al. Increasing omission of radiation therapy and sentinel node biopsy in elderly patients with early stage, hormone-positive breast cancer. Breast J. 2020;26(2):133–8. https://doi.org/10.1111/tbj.13483Retrospective analysis that found that since the Choosing Wisely ® guidelines have been released, there has been a decrease in the use of adjuvant radiation and nodal staging for women >70 years of age with early-stage, hormone-receptor positive breast cancer.
• Tamirisa N, Thomas SM, Fayanju OM, et al. Axillary nodal evaluation in elderly breast cancer patients: potential effects on treatment decisions and survival. Ann Surg Oncol. 2018;25(10):2890–8. https://doi.org/10.1245/s10434-018-6595-2. Analysis of the NCDB that revealed that older patients with node positive disease were more likely to receive adjuvant therapies with improved overall survival.
• Sun SX, Hollenbeak CS, Leung AM. Deviation from the standard of care for early breast cancer in the elderly: what are the consequences? Ann Surg Oncol. 2015;22(8):2492–9. https://doi.org/10.1245/s10434-014-4290-5. SEER database analysis which demonstrated that as women age, those with Stage 1 cancer are less likely to receive standard care and may negatively impact survival.
Hamaker ME, Bastiaannet E, Evers D, Water W, Smorenburg CH, Maartense E, et al. Omission of surgery in elderly patients with early stage breast cancer. Eur J Cancer. 2013;49(3):545–52. https://doi.org/10.1016/j.ejca.2012.08.010.
Kimmick GG, Major B, Clapp J, Sloan J, Pitcher B, Ballman K, et al. Using ePrognosis to estimate 2-year all-cause mortality in older women with breast cancer: Cancer and Leukemia Group B (CALGB) 49907 and 369901 (Alliance A151503). Breast Cancer Res Treat. 2017;163(2):391–8. https://doi.org/10.1007/s10549-017-4188-6.
University of California San Francisco. ePrognosis. https://eprognosis.ucsf.edu/index.php. Accessed 29 June 2020.
Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25(14):1824–31. https://doi.org/10.1200/JCO.2007.10.6559.
Hind D, Wyld L, Beverley CB, Reed MW. Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus). Cochrane Database Syst Rev. 2006;(1):CD004272. Published 2006 Jan 25. https://doi.org/10.1002/14651858.CD004272.pub2.
Garimella V, Hussain T, Agarwal V, Radhakrishna S, Fox JN, Kneeshaw PJ, et al. Clinical response to primary letrozole therapy in elderly patients with early breast cancer: possible role for p53 as a biomarker. Int J Surg. 2014;12(8):821–6. https://doi.org/10.1016/j.ijsu.2014.06.009.
de Glas NA, Jonker JM, Bastiaannet E, de Craen AJ, van de Velde CJ, Siesling S, et al. Impact of omission of surgery on survival of older patients with breast cancer. Br J Surg. 2014;101(11):1397–404. https://doi.org/10.1002/bjs.9616.
•• Johnston SJ, Kenny FS, Syed BM, Robertson JF, Pinder SE, Winterbottom L, et al. A randomised trial of primary tamoxifen versus mastectomy plus adjuvant tamoxifen in fit elderly women with invasive breast carcinoma of high oestrogen receptor content: long-term results at 20 years of follow-up. Ann Oncol. 2012;23(9):2296–300. https://doi.org/10.1093/annonc/mdr630Long-term follow-up of 153 elderly patients with early, node-negative hormone-receptor positive, breast cancer were randomized to tamoxifen or tamoxifen and surgery. There was no difference in recurrence, metastasis, disease-specific or overall survival, but the tamoxifen only group did have higher failure rates for local control.
• Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, Taylor C, Arriagada R, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–16. https://doi.org/10.1016/S0140-6736(11)61629-2. Meta-analysis that found after breast-conserving surgery, radiation therapy halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth.
Weberpals J, Jansen L, Müller OJ, Brenner H. Long-term heart-specific mortality among 347,476 breast cancer patients treated with radiotherapy or chemotherapy: a registry-based cohort study. Eur Heart J. 2018;39(43):3896–903. https://doi.org/10.1093/eurheartj/ehy167.
Taylor C, Correa C, Duane FK, Aznar MC, Anderson SJ, Bergh J, et al. Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. Version 2. J Clin Oncol. 2017;35(15):1641–9. https://doi.org/10.1200/JCO.2016.72.0722.
• Arraras JI, Manterola A, Illarramendi JJ, Asin G, de la Cruz S, Ibañez B, et al. Quality of life evolution in elderly survivors with localized breast cancer treated with radiotherapy over a three-year follow-up. Breast. 2018;41:74–81. https://doi.org/10.1016/j.breast.2018.06.010. In older breast cancer patients, quality of life did not vary by local treatment type.
•• Manyam BV, Tendulkar R, Cherian S, Vicini F, Badiyan SN, Shah C. Evaluating candidacy for hypofractionated radiation therapy, accelerated partial breast irradiation, and endocrine therapy after breast conserving surgery: a Surveillance Epidemiology and End Results (SEER) analysis. Am J Clin Oncol. 2018;41(6):526–31. https://doi.org/10.1097/COC.0000000000000332Analysis of the SEER database that showed a large portion of older women with early-stage breast cancer are eligible for shorter courses of radiation therapy, or omission of radiation therapy when appropriately applying guidelines and clinical trial inclusion criteria.
• Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362(6):513–20. https://doi.org/10.1056/NEJMoa0906260. Ten year follow-up of early stage breast cancer patients which found that accelerated, hypofractionated whole-breast irradiation was not inferior to standard radiation treatment in women who underwent lumpectomy.
Sanz J, Zhao M, Rodríguez N, Granado R, Foro P, Reig A, et al. Once-weekly hypofractionated radiotherapy for breast cancer in elderly patients: efficacy and tolerance in 486 patients. Biomed Res Int. 2018;2018:8321871–9. https://doi.org/10.1155/2018/8321871.
Fiorentino A, Gregucci F, Mazzola R, Figlia V, Ricchetti F, Sicignano G, et al. Intensity-modulated radiotherapy and hypofractionated volumetric modulated arc therapy for elderly patients with breast cancer: comparison of acute and late toxicities. Radiol Med. 2019;124(4):309–14. https://doi.org/10.1007/s11547-018-0976-2.
Cante D, Petrucci E, Sciacero P, Piva C, Ferrario S, Bagnera S, et al. Ten-year results of accelerated hypofractionated adjuvant whole-breast radiation with concomitant boost to the lumpectomy cavity after conserving surgery for early breast cancer. Med Oncol. 2017;34(9):152. https://doi.org/10.1007/s12032-017-1020-4.
• De Santis MC, Bonfantini F, Di Salvo F, Fiorentino A, Dispinzieri M, Caputo M, et al. Hypofractionated whole-breast irradiation with or without boost in elderly patients: clinical evaluation of an Italian experience. Clin Breast Cancer. 2018;18(5):e1059–66. https://doi.org/10.1016/j.clbc.2018.04.003. Prospective clinical trial in older patients which demonstrated that that hypofractionated radiation therapy is effective and well tolerated. Routine boost in patients over 65 is not justified.
Rovea P, Fozza A, Franco P, De Colle C, Cannizzaro A, Di Dio A, et al. Once-weekly hypofractionated whole-breast radiotherapy after breast-conserving surgery in older patients: a potential alternative treatment schedule to daily 3-week hypofractionation. Clin Breast Cancer. 2015;15(4):270–6. https://doi.org/10.1016/j.clbc.2014.12.011.
•• Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, et al. Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol. 2017;7(2):73–9. https://doi.org/10.1016/j.prro.2016.09.007ASTRO guidelines for those patients who are suitable candidates for APBI.
•• Whelan TJ, Julian JA, Berrang TS, Kim DH, Germain I, Nichol AM, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019;394(10215):2165–72. https://doi.org/10.1016/S0140-6736(19)32515-2Randomized controlled clinical trial that found external beam ABPI was non-inferior to whole-breast radiation, but did have higher rates of moderate late toxicity and poorer cosmesis.
Ott OJ, Strnad V, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, et al. GEC-ESTRO multicenter phase 3-trial: accelerated partial breast irradiation with interstitial multicatheter brachytherapy versus external beam whole breast irradiation: early toxicity and patient compliance. Radiother Oncol. 2016;120(1):119–23. https://doi.org/10.1016/j.radonc.2016.06.019.
Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014;383(9917):603–13. https://doi.org/10.1016/S0140-6736(13)61950-9 Erratum in: Lancet. 2014 Feb 15;383(9917):602.
Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomized controlled equivalence trial. Lancet Oncol. 2013;14:1269–77.
Vaidya JS, Bulsara M, Saunders C, Flyger H, Tobias JS, Corica T, et al. Effect of delayed targeted intraoperative radiotherapy vs whole-breast radiotherapy on local recurrence and survival: long-term results from the TARGIT-A randomized clinical trial in early breast cancer. JAMA Oncol. 2020:e200249. https://doi.org/10.1001/jamaoncol.2020.0249.
Jacobs DHM, Horeweg N, Straver M, Roeloffzen EMA, Speijer G, Merkus J, et al. Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique. Breast. 2019;46:32–9. https://doi.org/10.1016/j.breast.2019.04.006.
Jacobs DHM, Speijer G, Petoukhova AL, Roeloffzen EMA, Straver M, Marinelli A, et al. Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients. Breast Cancer Res Treat. 2018;169(3):549–59. https://doi.org/10.1007/s10549-018-4712-3.
Abbott AM, Valente SA, Loftus L, Tendulkar RD, Greif JM, Bethke KP, et al. A multi-institutional analysis of intraoperative radiotherapy for early breast cancer: does age matter? Am J Surg. 2017;214(4):629–33. https://doi.org/10.1016/j.amjsurg.2017.06.018.
•• National Institutes of Health, ClinicalTrials.gov. Prospective phase II study of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer (TARGIT-E). https://clinicaltrials.gov/ct2/show/NCT01299987. Accessed 13 July 2020. Ongoing clinical trial that will evaluate the safety and efficiacy of IORT in women age ≥70 with small, hormone-receptor positive, node negative tumors.
Paulsson AK, Fowble B, Lazar AA, Park C, Sherertz T. Radiotherapy utilization for patients over age 60 with early stage breast cancer. Clin Breast Cancer. 2020;20(2):168–73. https://doi.org/10.1016/j.clbc.2019.10.005.
Bazan JG, Fisher JL, Park KU, Marcus EA, Bittoni MA, White JR. Assessing the impact of CALGB 9343 on surgical trends in elderly-women with stage I ER+ breast cancer: a SEER-based analysis. Front Oncol. 2019;9:621. https://doi.org/10.3389/fonc.2019.00621.
Palta M, Palta P, Bhavsar NA, Horton JK, Blitzblau RC. The use of adjuvant radiotherapy in elderly patients with early-stage breast cancer: changes in practice patterns after publication of Cancer and Leukemia Group B 9343. Cancer. 2015;121(2):188–93. https://doi.org/10.1002/cncr.28937.
• Cortina CS, Agarwal S, Mulder LL, Poirier J, Rao R, Ansell DA, et al. Are providers and patients following hormonal therapy guidelines for patients over the age of 70? The influence of CALGB 9343. Clin Breast Cancer. 2018;18(6):e1289–92. https://doi.org/10.1016/j.clbc.2018.07.004. Retrospective cohort study that found older early stage breast cancer patients, increase age was associated with no receiving hormonal therapy, usually due to lack of benefit by providers.
Nichol AM, Chan EK, Lucas S, Smith SL, Gondara L, Speers C, et al. The use of hormone therapy alone versus hormone therapy and radiation therapy for breast cancer in elderly women: a population-based study. Int J Radiat Oncol Biol Phys. 2017;98(4):829–39. https://doi.org/10.1016/j.ijrobp.2017.02.094.
Dispinzieri M, La Rocca E, Meneghini E, Fiorentino A, Lozza L, Di Cosimo S, et al. Discontinuation of hormone therapy for elderly breast cancer patients after hypofractionated whole-breast radiotherapy. Med Oncol. 2018;35(7):107. https://doi.org/10.1007/s12032-018-1165-9.
Chesney TR, Yin JX, Rajaee N, Tricco AC, Fyles AW, Acuna SA, et al. Tamoxifen with radiotherapy compared with tamoxifen alone in elderly women with early-stage breast cancer treated with breast conserving surgery: a systematic review and meta-analysis. Radiother Oncol. 2017;123(1):1–9. https://doi.org/10.1016/j.radonc.2017.02.019.
• Matuschek C, Bölke E, Haussmann J, Mohrmann S, Nestle-Krämling C, Gerber PA, et al. The benefit of adjuvant radiotherapy after breast conserving surgery in older patients with low risk breast cancer- a meta-analysis of randomized trials. Radiat Oncol. 2017;12(1):60. https://doi.org/10.1186/s13014-017-0796-x. Meta-analysis which found that radiation therapy reduced local recurrence in older breast cancer patients with low-risk tumors, but did not improve overall survival.
Inoue H, Hirano A, Ogura K, Kamimura M, Hattori A, Yukawa H, et al. Breast-conserving surgery without radiation in elderly women with early breast cancer. Surg Oncol. 2019;31:22–5. https://doi.org/10.1016/j.suronc.2019.08.008.
Tang L, Matsushita H, Jingu K. Controversial issues in radiotherapy after breast-conserving surgery for early breast cancer in older patients: a systematic review. J Radiat Res. 2018;59(6):789–93. https://doi.org/10.1093/jrr/rry071.
Cortina CS, Woodfin AA, Tangalakis LL, Wang X, Son JD, Poirier J, et al. Treating positive axillary disease in elderly breast cancer patients: the impact of age on radiation therapy. Breast Care. 2020. In press. https://doi.org/10.1159/000508243.
•• Eaton BR, Jiang R, Torres MA, Kahn ST, Godette K, Lash TL, et al. Benefit of adjuvant radiotherapy after breast-conserving therapy among elderly women with T1-T2N0 estrogen receptor-negative breast cancer. Cancer. 2016;122(19):3059–68. https://doi.org/10.1002/cncr.30142Retrospective review of the SEER database examining women age ≥70 with T1-T2, node negative, hormone-receptor negative breast cancer found that those women who had radiation therapy, had lower incidence of breast cancer death at years.
• Daugherty EC, Daugherty MR, Bogart JA, Shapiro A. Adjuvant radiation improves survival in older women following breast-conserving surgery for estrogen receptor-negative breast cancer. Clin Breast Cancer. 2016;16(6):500–506.e2. https://doi.org/10.1016/j.clbc.2016.06.017. SEER database analysis that found in older women with T1 hormone receptor positive tumor, the addition of radiation therapy did improve survival.
Valli M, Cima S, Fanti P, Muoio B, Vanetti A, Azinwi CN, et al. The role of radiotherapy in elderly women with early-stage breast cancer treated with breast conserving surgery. Tumori. 2018;104(6):429–33. https://doi.org/10.1177/0300891618792465.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The author has no relevant disclosures to report. This article does not contain any studies with human or animal subjects performed by any of the authors. The Author ICJME COI is included separately.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Local-Regional Evaluation and Therapy
Rights and permissions
About this article
Cite this article
Cortina, C.S. De-Escalation of Local-Regional Therapy for Older Breast Cancer Patients. Curr Breast Cancer Rep 12, 344–350 (2020). https://doi.org/10.1007/s12609-020-00395-8
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12609-020-00395-8