Introduction: Breast cancer is the second most common cause of cancer death in females, and 30% of these patients are over the age of 70 years. Studies have shown deviation from the standard treatment paradigms in the elderly, especially in regard to radiation treatment. Methods: We performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital to examine which patient factors influenced radiotherapy. Results: Increasing patient age was associated with a decrease in the probability of receiving radiotherapy, while HER2-negative patients were more likely to receive radiation. Neither race, number of coexisting medical conditions, or insurance status showed any influence on radiation treatment. Conclusion: Patient age has a significant influence if elderly patients with axillary disease receive radiotherapy. Further investigation and validation are needed to understand why chronological age rather than biological age influences treatment modalities.

Breast cancer is the second most common cancer in women, after skin cancer, and in the United States alone, there are 266,000 new cases estimated to be diagnosed in 2018 [1]. One-third of these new cases will be diagnosed in women >70 years of age [2]. Treatment of breast cancer has made tremendous strides over the past 2 decades, and while the absolute risk of death has decreased by 15.3% for women aged 50–64 years, the absolute risk of death has only decreased by 7.5% for women aged 75 years and older [3, 4]. While guidelines are in place regarding breast cancer treatment in the elderly, they remain controversial and leave much room for interpretation.

At our institution, an academic tertiary referral center in a major metropolitan area, we treat approximately 600 patients with breast cancer annually. Of those, approximately 5–7% are over the age of 70 years. We performed a retrospective chart review on breast cancer patients over the age of 70 years with pathologically proven axillary disease to examine which characteristics influence radiotherapy in this patient subset.

All patients diagnosed with breast cancer and pathologically proven axillary disease over the age of 70 years who were treated at our institution between April 2008 and September 2016 were included. Positive axillary disease was defined as any evidence of disease on final axillary pathology (including sentinel node biopsy or axillary lymph node dissection), including those patients with disease seen on immunohistochemical staining and those with microscopic disease. To examine treatment choices among the elderly with breast cancer, as well as variables that may predict those choices, data was collected on a total 116 women and 2 men (n = 118) after approval by our Institutional Review Board.

For the potential predictive variables, means and SDs were calculated for age and number of previous medical problems, while counts and percentages were tabulated for gender, race/ethnicity, family history of breast cancer, laterality, recurrence, estrogen receptor (ER) status, progesterone receptor (PR) status, receptor tyrosine-protein kinase erbB-2 (HER2/neu) status, and type of insurance. Counts and percentages were also tabulated for whether the patient received radiation therapy (RT).

Before predictive analyses were undertaken, a correlation matrix was created to analyze if there were relationships among predictive variables by using the Holm-Bonferroni correction for the family-wise error rate. Then a series of hypothesis tests were performed, using t tests for continuous variables (age and number of previous medical problems) and Fisher exact tests for categorical or binary variables (race/ethnicity, family history of breast cancer, laterality, recurrence, ER status, PR status, HER2/neu status, and type of insurance [gender was not examined due to there being too few males in the sample (n = 2)]) in relation to RT. To examine whether there were any other confounding differences between the 2 separate age groups seen in RT, further statistical analysis was performed. To examine differences on (1) hormone receptor status, Fisher exact tests were conducted; (2) on number of comorbidities, a Welch’s t test was performed; and (3) on tumor stage, a Mann-Whitney test was performed.

Due to the large number of hypothesis tests, the false discovery rate was controlled at 0.05 using a Benjamini-Hochberg correction. All analyses were conducted in R 3.3.2 [5].

Within this cohort of patients, age ranged from 70 to 92 years with a mean ± SD of 78 ± 5.4. On average, patients had 7.8 medical conditions (SD 4.6) which were listed in the patient’s “problem list” or “past medical history” in their electronic medical record (Tables 1, 2).

Table 1.

Counts (%) of the categorical predictive variables for the entire sample

Counts (%) of the categorical predictive variables for the entire sample
Counts (%) of the categorical predictive variables for the entire sample
Table 2.

Categorical predictive variables by radiation therapy choice

Categorical predictive variables by radiation therapy choice
Categorical predictive variables by radiation therapy choice

In total, 55% of patients underwent RT (defined as whole breast radiotherapy with or without nodal radiation). While increasing patient age was associated with a decrease in the probability of receiving RT (Fig. 1), no other factors were associated with a lower likelihood of receiving radiotherapy. Patients who were HER2-negative were associated with an increased likelihood to receive RT independently of age. Thus, patient age and HER2/neu-negative status were statistically significant in the prediction of RT (Table 3).

Table 3.

Odds ratios and their CIs for age and HER2/neu status for receiving radiation therapy

Odds ratios and their CIs for age and HER2/neu status for receiving radiation therapy
Odds ratios and their CIs for age and HER2/neu status for receiving radiation therapy
Fig. 1.

Age by radiation.

Fig. 1.

Age by radiation.

Close modal

Based on the results of this set of hypothesis tests, nested logistic regression models were created using age and HER2/neu status. The nested models were then tested using likelihood ratio tests. The final model included both age and recurrence. Patients over the age of 84 years had a statistically significantly lower rate of receiving RT (p < 0.001). Notably, after the age of 84 years, only 16.7% of patients received RT, as opposed to 61.0% of those aged 84 years or younger.

There were no significant differences found between any of the age groups examined on any of the measures, thus allowing the 2 age groups to be comparable in terms of tumor biology, tumor stage, and patient medical comorbidities. Neither race, gender, or insurance status showed any role in influencing which type of therapy or therapies a patient received.

On subset analysis, 46 patients (39% of the patient group) underwent breast conservation therapy (BCT) with 33 (71.7%) of these patients receiving RT, while 54 (45.8%) underwent mastectomy with 25 (46.3%) of these patients receiving RT. Seventeen patients did not undergo surgery, and 1 patient underwent axillary dissection alone (without any breast surgery). On χ2 analysis, a comparison of receiving RT between the BCT and mastectomy groups is statistically significant with p = 0.010. Clinically speaking, patients who underwent BCT in this cohort were more likely to receive RT compared to those that underwent mastectomy.

Elderly patients with breast cancer are often undertreated, despite accounting for other patient variables [2]. There are a multitude of reasons why differences in care exist between varying age groups, and many inconsistencies exist amongst studies as to why these variations occur. Elderly women frequently have more favorable tumor biology as defined by histologically low grade, ER and PR receptor-positive, and HER2-negative tumors [6-11]. Treatment for this age group commonly does not adhere to standard guidelines and, therefore, patients have lower rates of receiving standard therapies. Surgically, elderly patients are also less likely to receive the standard of care, and many do not receive RT after breast-conserving surgery [12].

Elderly patients may have higher rates of comorbidities, poorer performance status, less social support, concerns about quality of life, and a lower life expectancy, which can all contribute to why there is nonstandardization [13]. All of these variables may influence a clinician’s treatment plan and support the decision to deviate from standard protocols. In the surgical management of breast cancer, elderly patients are usually considered more appropriate candidates for BCT over mastectomy given the ability to avoid general anesthesia with shorter operative time duration. However, adjuvant RT is standard of care in patients undergoing BCT, and this component of therapy should only be omitted due to age after thoughtful consideration as well as patient education and discussion. Long-term follow-up of the CALGB 9343 study showed that in patients over the age of 70 years with early-stage, node-negative, ER/PR-positive tumors who underwent BCT and received 5 years of hormonal therapy, adjuvant RT could be safely omitted without significant change in time to distant metastasis, breast cancer-specific survival, or overall survival [13].

De-escalation studies and trials do not typically include patients with axillary disease involvement; however, Martelli et al. [14, 15] were the exception to this statement. The team investigated if sentinel node biopsy and axillary dissection was useful in clinically node-negative elderly breast cancer patients and found no difference in breast cancer or overall survival. The authors encouraged clinicians to reserve axillary surgery for those patients who developed overt clinically apparent axillary disease.

RT is not without toxicity, and this is especially notable for elderly patients who are more likely to have lower functional status when entering treatment. For example, cardiac complications, such as ischemia, are a concern in this population and may support decisions for omission or reduction of radiotherapy [16]. Furthermore, the time commitment and mobility required from patients undergoing RT may not be suitable or as manageable for this age group. Yet, when faced with a cancer at high risk of locoregional recurrence (LRR), or those not amenable to treatment with endocrine therapy alone, complete omission of RT is suboptimal.

More recent trends in radiation oncology involve modification of radiotherapy techniques for elderly patients so that treatment duration is reduced but not entirely omitted. Some of these modifications consist of partial breast irradiation, hypofractionated RT, and omitting the boost therapy to the tumor bed [17]. Prior authors have shown LRR rates similar to those of whole breast irradiation in properly chosen patients for partial breast irradiation [18-22]. Of note, the patients in these studies have favorable disease burden with tumor size <2 cm and node-negative disease, among other low-risk features of tumor biology [23].

However, these studies do not address the disparities in radiotherapy in the elderly with more advanced disease or more aggressive tumor features. Currently, there is a single clinical trial in the United States that is recruiting patients to compare hypofractionated radiotherapy to conventional whole breast irradiation in axillary node-positive patients (NCT02690636) with the primary outcome of examining LRR at 5 years [17]. Despite the fact that elderly patients (defined as age >65 years) are not being included in this phase 3 trial, the results may be beneficial and applicable to this population.

Previous studies have shown that chronologic age has been associated with substandard therapy, independent of performance status or comorbidities, and physicians may be undertreating even healthy older women [24-27]. With an increasing overall life expectancy causing an ever-growing aging population, the treatment algorithm of elderly breast cancer patients is of paramount importance to simultaneously increase disease-free survival while minimizing the morbidity of therapy. While various guidelines exist to influence clinical decisions in this patient population, there is still sparse and variable evidence for the variation in treatment pathways.

Studies over the past 2 decades show conflicting evidence on whether the addition of adjuvant RT benefits breast cancer patients by increasing the rates of disease-free survival and overall survival; however, current studies consistently confirm a benefit in reducing the LRR amongst all age groups [28-32] (Table 4). Notably, both the Australian Breast and Colorectal Cancer Study Group (ABCSG) 8A randomized clinical trial and a separate meta-analysis demonstrated a clinically and statistically significant difference in overall survival for those that received RT compared to those that did not [29, 33-36]. However, limitations to these studies include the inconsistency of nodal status in inclusion criteria and the inconsistency of patient age in both inclusion criteria and data analyzation, making this data difficult to directly apply to elderly breast cancer patients with known axillary disease. This further demonstrates why more direct evidence is needed to appropriately guide treatment in this unique demographic age group.

Table 4.

Summary of randomized clinical trials on radiation treatment which included elderlya breast cancer patients

Summary of randomized clinical trials on radiation treatment which included elderlya breast cancer patients
Summary of randomized clinical trials on radiation treatment which included elderlya breast cancer patients

The authors of the PRIME and PRIME II studies specifically examined the benefit of RT in women aged 65 years and older. The authors of PRIME found that there was no difference in quality of life of women who received RT compared to those who did not; there was a small benefit in the reduction of the LRR rate at 5 years, but at 15 months, the addition of RT was considered to be cost-ineffective. With the current environment of healthcare and payers (both private and governmental provided insurance plans) in the United States, the cost-benefit is of substantial significance [37, 38].

The trend of undertreatment in this age group also exists at our institution as evident by lower rates of RT with increasing age. As discussed above, perhaps the more appropriate course of action is consideration for modified radiotherapy treatment in elderly patients rather than omission, especially in those with high functional status and long life expectancy.

Due to the retrospective nature of this analysis, no distinction between whole breast radiation and/or nodal irradiation was made. Notably, there was 1 patient in our cohort that had isolated axillary disease and received nodal radiation alone. Longitudinal prospective data regarding LRR, disease-free survival, and overall survival could also not be adequately analyzed; however, the authors do plan an analysis in the next several years, when complete 5-year survival analyses are available for this patient cohort. Treatment decisions were difficult to analyze because of the heterogenous documentation of providers. Because of this, patient compliance with therapy recommendations could also not be adequately studied.

The age of 70 years has been quantified by several previous authors and society guidelines to be the age by which patients are considered “elderly.” This number is fairly arbitrary and based more on life expectancy and clinical art rather than evidence-based science. Life expectancy varies between countries and continents and should be included into a multidisciplinary approach in designing the treatment plan for these patients. With advances in medicine, life expectancy will most likely be shifted during the upcoming decades. There is little consensus on the management of elderly breast cancer patients regarding when de-escalation is truly appropriate, specifically concerning administration of RT in those with axillary disease. As more evidence will be discovered through future studies focusing on management decisions specifically in elderly breast cancer patients, we will be able to more precisely define treatment paradigms. But perhaps more importantly, biological age rather than chronological age should be the most important factor for this population, and clinicians should consider validated functional status scores in their overall patient assessment.

Without data to support a standardized protocol for treating elderly women, physicians will likely continue treatment on a case-to-case basis with various guidelines to steer clinical practice. Factors that influence physicians’ treatment decisions warrant further investigation and are currently being investigated by the authors. As more prospective and retrospective studies emerge regarding the treatment of breast cancer in the elderly, we anticipate stronger evidence-based treatment protocols and algorithms will be developed.

The authors thank Karen Ohara for her dedication and assistance in facilitating institutional approval of the study.

This project was approved by the Institutional Review Board (IRB) at Rush University Medical Center. Consent for patient participation was waived at the approval of this study by the IRB in order to complete this study, given that it was a retrospective chart review of the electronic medical record. No consent for publication is required, as no individual’s data is referenced in this article. No animal research was performed in this study.

The authors have no conflicts of interest to declare.

This study has no source of funding to be disclosed.

C.S.C. was the predominant author of the manuscript and also contributed greatly to the data collection, analysis, and manuscript editing. A.A.W. contributed to data collection, manuscript creation and revision, as well as editing. L.L.T. assisted with data collection, manuscript creation, and editing. X.W. and J.D.S. helped with data collection and manuscript editing. J.P. was the predominant contributor to data analysis. R.R. and K.K. contributed to project development and manuscript editing. A.M. contributed greatly to project development, as well as manuscript creation, revision, and editing.

1.
American Cancer Society
. (
2018
). Cancer Facts & Figures 2018. 2018. https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html. Accessed February 14, 2018.
2.
Tesarova
P
.
Breast cancer in the elderly-Should it be treated differently?
Rep Pract Oncol Radiother
.
2012
Jul
;
18
(
1
):
26
33
.
[PubMed]
1507-1367
3.
Karuturi
M
,
VanderWalde
N
,
Muss
H
.
Approach and management of breast cancer in the elderly
.
Clin Geriatr Med
.
2016
Feb
;
32
(
1
):
133
53
.
[PubMed]
0749-0690
4.
National Cancer Institute
.
SEER cancer statistics factsheets: breast cancer.
2015
. http://seer.cancer.gov/statfacts/html/breast.html. Accessed August 5, 2017.
5.
R Core Team
. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.
2016
. https://www.R-project.org. Accessed June 3, 2017.
6.
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
Apr
;
123
(
1
):
1
9
.
[PubMed]
0167-8140
7.
Diab
SG
,
Elledge
RM
,
Clark
GM
.
Tumor characteristics and clinical outcome of elderly women with breast cancer
.
J Natl Cancer Inst
.
2000
Apr
;
92
(
7
):
550
6
.
[PubMed]
0027-8874
8.
Gennari
R
,
Curigliano
G
,
Rotmensz
N
,
Robertson
C
,
Colleoni
M
,
Zurrida
S
, et al
Breast carcinoma in elderly women: features of disease presentation, choice of local and systemic treatments compared with younger postmenopasual patients
.
Cancer
.
2004
Sep
;
101
(
6
):
1302
10
.
[PubMed]
0008-543X
9.
Rodrigues
NA
,
Dillon
D
,
Carter
D
,
Parisot
N
,
Haffty
BG
.
Differences in the pathologic and molecular features of intraductal breast carcinoma between younger and older women
.
Cancer
.
2003
Mar
;
97
(
6
):
1393
403
.
[PubMed]
0008-543X
10.
Davies
C
,
Godwin
J
,
Gray
R
,
Clarke
M
,
Cutter
D
,
Darby
S
, et al;
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)
.
Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials
.
Lancet
.
2011
Aug
;
378
(
9793
):
771
84
.
[PubMed]
0140-6736
11.
Fisher
B
,
Costantino
J
,
Redmond
C
,
Poisson
R
,
Bowman
D
,
Couture
J
, et al
A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors
.
N Engl J Med
.
1989
Feb
;
320
(
8
):
479
84
.
[PubMed]
0028-4793
12.
Giordano
SH
,
Hortobagyi
GN
,
Kau
SW
,
Theriault
RL
,
Bondy
ML
.
Breast cancer treatment guidelines in older women
.
J Clin Oncol
.
2005
Feb
;
23
(
4
):
783
91
.
[PubMed]
0732-183X
13.
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
Jul
;
31
(
19
):
2382
7
.
[PubMed]
0732-183X
14.
Martelli
G
,
Boracchi
P
,
De Palo
M
,
Pilotti
S
,
Oriana
S
,
Zucali
R
, et al
A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up
.
Ann Surg
.
2005
Jul
;
242
(
1
):
1
6
.
[PubMed]
0003-4932
15.
Martelli
G
,
Miceli
R
,
Daidone
MG
, et al
Axillary dissection versus no axillary dissection in elderly patients with breast cancer and no palpable axillary nodes: results after 15 years of follow-up.
Annals of Surgical Oncology.
2011
. Jan;18(1):125-33.
16.
Darby
SC
,
Ewertz
M
,
McGale
P
,
Bennet
AM
,
Blom-Goldman
U
,
Brønnum
D
, et al
Risk of ischemic heart disease in women after radiotherapy for breast cancer
.
N Engl J Med
.
2013
Mar
;
368
(
11
):
987
98
.
[PubMed]
0028-4793
17.
Hansen
TM
,
Zellars
RC
.
Treatment Minimization in Older Patients With Early-Stage Breast Cancer
.
Cancer J
.
2017
Jul/Aug
;
23
(
4
):
231
7
.
[PubMed]
1528-9117
18.
Ott
OJ
,
Strnad
V
,
Hildebrandt
G
,
Kauer-Dorner
D
,
Knauerhase
H
,
Major
T
, et al;
Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO)
.
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
Jul
;
120
(
1
):
119
23
.
[PubMed]
0167-8140
19.
Shah
C
,
Badiyan
S
,
Ben Wilkinson
J
,
Vicini
F
,
Beitsch
P
,
Keisch
M
, et al
Treatment efficacy with accelerated partial breast irradiation (APBI): final analysis of the American Society of Breast Surgeons MammoSite(®) breast brachytherapy registry trial
.
Ann Surg Oncol
.
2013
Oct
;
20
(
10
):
3279
85
.
[PubMed]
1068-9265
20.
Livi
L
,
Meattini
I
,
Marrazzo
L
,
Simontacchi
G
,
Pallotta
S
,
Saieva
C
, et al
Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial
.
Eur J Cancer
.
2015
Mar
;
51
(
4
):
451
63
.
[PubMed]
0959-8049
21.
Rabinovitch
R
,
Moughan
J
,
Vicini
F
,
Pass
H
,
Wong
J
,
Chafe
S
, et al
Long-term update of NRG Oncology RTOG 0319: a phase 1 and 2 trial to evaluate 3-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for stage I and II breast carcinoma
.
Int J Radiat Oncol Biol Phys
.
2016
Dec
;
96
(
5
):
1054
9
.
[PubMed]
0360-3016
22.
White
J
,
Winter
K
,
Kuske
RR
,
Bolton
JS
,
Arthur
DW
,
Scroggins
T
, et al
Long-term cancer outcomes from study NRG Oncology/RTOG 9517: a phase 2 study of accelerated partial breast irradiation with multicatheter brachytherapy after lumpectomy for early- stage breast cancer
.
Int J Radiat Oncol Biol Phys
.
2016
Aug
;
95
(
5
):
1460
5
.
[PubMed]
0360-3016
23.
Smith
BD
,
Arthur
DW
,
Buchholz
TA
,
Haffty
BG
,
Hahn
CA
,
Hardenbergh
PH
, et al
Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO)
.
Int J Radiat Oncol Biol Phys
.
2009
Jul
;
74
(
4
):
987
1001
.
[PubMed]
0360-3016
24.
Goodwin
JS
,
Hunt
WC
,
Samet
JM
.
Determinants of cancer therapy in elderly patients
.
Cancer
.
1993
Jul
;
72
(
2
):
594
601
.
[PubMed]
0008-543X
25.
Silliman
RA
,
Troyan
SL
,
Guadagnoli
E
,
Kaplan
SH
,
Greenfield
S
.
The impact of age, marital status, and physician-patient interactions on the care of older women with breast carcinoma
.
Cancer
.
1997
Oct
;
80
(
7
):
1326
34
.
[PubMed]
0008-543X
26.
Silliman
RA
,
Guadagnoli
E
,
Weitberg
AB
,
Mor
V
.
Age as a predictor of diagnostic and initial treatment intensity in newly diagnosed breast cancer patients
.
J Gerontol
.
1989
Mar
;
44
(
2
):
M46
50
.
[PubMed]
0022-1422
27.
Mandelblatt
JS
,
Hadley
J
,
Kerner
JF
,
Schulman
KA
,
Gold
K
,
Dunmore-Griffith
J
, et al
Patterns of breast carcinoma treatment in older women: patient preference and clinical and physical influences
.
Cancer
.
2000
Aug
;
89
(
3
):
561
73
.
[PubMed]
0008-543X
28.
Fyles
AW
,
McCready
DR
,
Manchul
LA
,
Trudeau
ME
,
Merante
P
,
Pintilie
M
, et al
Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer
.
N Engl J Med
.
2004
Sep
;
351
(
10
):
963
70
.
[PubMed]
0028-4793
29.
Pötter
R
,
Gnant
M
,
Kwasny
W
,
Tausch
C
,
Handl-Zeller
L
,
Pakisch
B
, et al;
Austrian Breast and Colorectal Cancer Study Group
.
Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer
.
Int J Radiat Oncol Biol Phys
.
2007
Jun
;
68
(
2
):
334
40
.
[PubMed]
0360-3016
30.
Sautter-Bihl
ML
,
Sedlmayer
F
,
Budach
W
,
Dunst
J
,
Feyer
P
,
Fietkau
R
, et al
When are breast cancer patients old enough for the quitclaim of local control?
Strahlenther Onkol
.
2012
Dec
;
188
(
12
):
1069
73
.
[PubMed]
0179-7158
31.
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
Mar
;
12
(
1
):
60
.
[PubMed]
1748-717X
32.
Blamey
RW
,
Bates
T
,
Chetty
U
,
Duffy
SW
,
Ellis
IO
,
George
D
, et al
Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial
.
Eur J Cancer
.
2013
Jul
;
49
(
10
):
2294
302
.
[PubMed]
0959-8049
33.
Budach
W
,
Bölke
E
,
Kammers
K
,
Gerber
PA
,
Nestle-Krämling
C
,
Matuschek
C
.
Adjuvant radiation therapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials- an update
.
Radiat Oncol
.
2015
Dec
;
10
(
1
):
258
.
[PubMed]
1748-717X
34.
Whelan
TJ
,
Olivotto
IA
,
Parulekar
WR
,
Ackerman
I
,
Chua
BH
,
Nabid
A
, et al;
MA.20 Study Investigators
.
Regional Nodal Irradiation in Early-Stage Breast Cancer
.
N Engl J Med
.
2015
Jul
;
373
(
4
):
307
16
.
[PubMed]
0028-4793
35.
Poortmans
P
,
Kouloulias
V
,
van Tienhoven
G
,
Collette
L
,
Struikmans
H
,
Venselaar
JL
, et al;
EORTC Radiation Oncology and Breast Cancer Groups
.
Quality assurance in the EORTC randomized trial 22922/10925 investigating the role of irradiation of the internal mammary and medial supraclavicular lymph node chain works
.
Strahlenther Onkol
.
2006
Oct
;
182
(
10
):
576
82
.
[PubMed]
0179-7158
36.
Hennequin
C
,
Bossard
N
,
Servagi-Vernat
S
,
Maingon
P
,
Dubois
JB
,
Datchary
J
, et al
Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy
.
Int J Radiat Oncol Biol Phys
.
2013
Aug
;
86
(
5
):
860
6
.
[PubMed]
0360-3016
37.
Prescott
RJ
,
Kunkler
IH
,
Williams
LJ
,
King
CC
,
Jack
W
,
van der Pol
M
, et al
A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population. The PRIME trial
.
Health Technol Assess
.
2007
Aug
;
11
(
31
):
1
149
.
[PubMed]
1366-5278
38.
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
.
Lancet Oncol
.
2015
Mar
;
16
(
3
):
266
73
.
[PubMed]
1470-2045
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.