- The study hypothesizes that fertility concerns contribute to poor tamoxifen adherence in young breast cancer patients. It analyzes factors influencing tamoxifen initiation and adherence in 528 young patients. - Results show fertility concerns and smoking were associated with non-initiation and non-adherence to tamoxifen therapy. Discussion of fertility occurred in only 30.7% of encounters and referral to fertility specialists was low. - The conclusions call for oncologists to address fertility concerns with young patients to improve tamoxifen adherence, and emphasize smoking cessation programs. Developing predictive models and educational interventions on fertility and tamoxifen were recommended as future directions.

1. Hypothesis
We hypothesize that fertility concerns may contribute to the poor
tamoxifen adherence observed among young breast cancer patients.
References
1. Partridge AH, Wang PS, Winer EP, Avorn J. Nonadherence to adjuvant tamoxifen therapy in women with
primary breast cancer. J Clin Oncol. Feb 15 2003;21(4):602-606.
2. Hershman DL, Kushi LH, Shao T, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy
in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. Sep 20 2010;28(27):4120-4128.
3. Gradishar WJ, Hellmund R. A rationale for the reinitiation of adjuvant tamoxifen therapy in women receiving
fewer than 5 years of therapy. Clin Breast Cancer. Jan 2002;2(4):282-286.
4. Partridge AH, Gelber S, Peppercorn J, et al. Web-based survey of fertility issues in young women with breast
cancer. J Clin Oncol. Oct 15 2004;22(20):4174-4183.
The Impact of Fertility Concerns on Tamoxifen Adherence in Young Women With Breast Cancer
Natalia C. Llarena, Samantha L. Estevez, Omar Nunez, Anna Kane, Joelle Straehla, Jacqueline S. Jeruss
Northwestern University Feinberg School of Medicine, Department of Surgery
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois
Results
Patient Characteristics
Aim
To evaluate patient- and provider-level factors that influence
tamoxifen adherence among breast cancer patients age 45 and
younger.
Future Directions
• Develop and validate a predictive model of tamoxifen adherence
for young women (<,45) with ER+ breast cancer, based on
physician and patient-level factors, including fertility.
• Develop and validate a predictive model of tamoxifen adherence
for young women (<,45) at high risk for breast cancer.
• Design fertility preservation education interventions for both
providers and patients that jointly address fertility and tamoxifen
adherence.
HR: 1.935
(95% CI: 1.213 – 4.098)
P = 0.0102
P = 0.0369
Conclusions
• For ER+ breast cancer patients age 45 and under, fertility concerns
and current smoking are associated with tamoxifen non-initiation and
non-adherence.
• Despite the importance of fertility to young cancer patients and
recommendations from the American Society of Clinical Oncology
stating that oncologists should discuss fertility with young patients,
referral rates to fertility specialists are low.
• Oncologists should engage their patients in discussion about fertility
as it relates to breast cancer treatment.
• Efforts to improve tamoxifen adherence among young breast cancer
patients should address fertility concerns as a possible modifiable
risk factor. Smoking cessation programs should also be
emphasized.
Acknowledgements
This work was supported by the Oncofertility Consortium NIH/
NICHD U54HD076188 and the Cancer Prevention and Control
Travel Scholarship Program from the Robert H. Lurie
Comprehensive Cancer Center of Northwestern University
Background
• ~23,000 women age 45 and younger are diagnosed with breast
cancer annually.
• For patients with ER+ breast cancer, treatment with a 5-year course
of the SERM tamoxifen results in a 47% reduction in annual
recurrence risk and a 26% reduction in annual mortality.1,2
• Despite substantial benefits, tamoxifen adherence rates are low,
particularly among young women. Poor adherence is associated with
increased mortality and higher rates of breast cancer recurrence.3
• Tamoxifen is a teratogen and pregnancy should be avoided during
the recommended 5-year duration of therapy.
• For women of childbearing age (i.e., < 45) who have developed
breast cancer, fertility may be an important part of healthcare
decision making. A survey of young breast cancer patients reported
that 57% were concerned about becoming infertile as a result of
treatment.4
• As fertility declines significantly after the age of 35, the considerable
length of recommended tamoxifen therapy may be a critical deterrent
to adherence.
• Studies on adjuvant tamoxifen adherence have not examined fertility
concerns as a potential reason for non-adherence.
HR: 2.267
(95% CI: 1.163 – 9.266)
P = 0.0252
Encounter
Number of Patients
Total Number of Patients: 528
Percent
Documented discussion with
provider about effects of
treatment on fertility
162
30.7%
Patients expressed an interest in
maintaining fertility at time of
diagnosis
114
21.6%
Patients offered a fertility
preservation appointment
127
24.1%
Fertility preservation
appointment
98
18.6%
Patient Characteristics
Number
Total Number of Patients: 528
Percent
Initiated tamoxifen
465
88.1%
Did not initiate tamoxifen
63
11.9%
Discontinued or non-adherent
67
12.7%
Age at diagnosis (range: 25-45; mean age
39)
< 36
115
21.8%
≥ 36
413
78.2%
Race
White
376
71.2%
Black
63
11.9%
Asian
38
7.2%
Mixed / Other
21
4.0%
Unknown
30
5.7%
Ethnicity
Hispanic or Latino
40
7.6%
Marital Status
Married
336
63.6%
Not married
188
35.6%
Unknown
4
0.8%
Insurance Status
Private insurance
454
86.0%
Public insurance or uninsured
74
14.0%
Education Level
College graduate or above
232
43.9%
Below college
61
11.6%
Unknown
235
44.5%
Parity
Nulliparous
197
37.3%
Parity ≥ 1
308
58.3%
Unknown
23
4.4%
Surgery
Lumpectomy
248
47.0%
Mastectomy
277
52.4%
No Surgery
3
0.6%
Chemotherapy
302
57.2%
Radiation
366
69.3%
Pathological Stage of Disease
Stage 0
102
19.3%
Stage 1
162
30.7%
Stage 2
191
36.2%
Stage 3
72
13.6%
Unknown
1
0.2%
Follow-up Discussion Themes with Non-Adherent Patients
Number of Patients
70 Patients Contacted
Side effects or concerns about potential side effects
49
Perceived little benefit
10
Held tamoxifen to become pregnant but did not initiate/resume
because of inadequate information
6
Currently off tamoxifen to attempt pregnancy; planning to
resume after childbearing
6
Held tamoxifen to become pregnant and later initiated/resumed
5
Would have stopped tamoxifen to attempt pregnancy if provider
had initiated a discussion about fertility
5
Became pregnant while taking tamoxifen
2
If patient had not pursued information about fertility
preservation, she would not have been adequately informed
2
Could not undergo fertility preservation due to financial concerns
2
Waiting to complete tamoxifen before attempting pregnancy
1
Methods
• Data were obtained with IRB approval from Northwestern’s EMR
systems to identify 864 women diagnosed with ER+ breast cancer
between 2007 and 2012.
• Patients were excluded if they were post-menopausal at time of
diagnosis, if tamoxifen was not recommended, if they were widely
metastatic at diagnosis, or if data about tamoxifen was
unavailable. The Log-rank (Mantel-Cox) test was used to compare
Kaplan-Meier curves and generate hazard ratios. Fisher’s exact and
Chi-square tests were used for categorical values.
• The study population included 528 patients. Each patient’s chart was
reviewed to evaluate patient and provider-level factors that influenced
tamoxifen initiation and adherence.
• Provider-level factors associated with this decision were evaluated
evaluated and include (1) whether tamoxifen was recommended, (2)
whether a conversation about tamoxifen-related fertility concerns was
initiated by the provider, and (3) whether a referral to a fertility
specialist was provided. Patient-level factors included (1) whether the
patient agreed to take tamoxifen and (2) the duration of tamoxifen
use. Factors associated with non-adherence were also examined.!
0
5
10
15
20
25
30
Stage 0
Stage 1
Stage 2
Stage 3
NumberofPatients
Stage
Early Discontinuation of Tamoxifen
and Stage
Early
Discontinuation
Patients
Early Discontinution
Patients with Fertility
Concerns
0
5
10
15
20
25
30
35
40
45
Stage 0
Stage 1
Stage 2
Stage 3
NumberofPatients
Stage
Non-Initiation of Tamoxifen
and Stage
Non-Initation
Patients
Non-Initiation
Patients with
Fertility Concerns
The Kaplan-Meier curves above demonstrate discontinuation and non-adherence in patients who initiated Tamoxifen. Patients
were censored at time of death, menopause, metastasis, cancer recurrence, or loss to follow-up. P values and hazard ratios
were calculated using the Log-rank (Mantel-Cox) test. HR = hazard ratio
Factors Associated with Non-Adherence
Tamoxifen Adherence Data
27%
9%
2%
61%
1%
Reasons for Early Discontinuation of Tamoxifen
Fertility concerns
Concern about potential side effects
Perceived little benefit
Side effects
Comorbid condition
29%
1%
39%
13%
13%
3%
2%
Reasons for Non-Initiation of Tamoxifen
Fertility concerns
Comorbid condition
Concerns about side effects
Perceived low risk
Patient declined
Desired alternative therapy
Long length of therapy
Physician / Patient Interactions