Lack of Knowledge of Hormone Receptor Status and Use of Endocrine Therapy in Invasive Breast Cancer

Abstract

Objective:

The aim of this study was to investigate the level of understanding in women with newly diagnosed invasive breast cancer of the key clinical features of their disease that are important determinants in treatment decision making.

Methods:

The 1684 women aged between 26 and 88 years at diagnosis enrolled in a 5-year cohort study were asked by questionnaire about their estrogen receptor (ER) and progesterone receptor (PR) status and about their past or current treatment with adjuvant endocrine therapy. Information was linked with their ER and PR status determined from the histopathology report. Logistic regression analysis was used to explore the relationship between age and education status and the likelihood of being able to correctly report hormone receptor status, as well as the relationship between the likelihood of receiving adjuvant endocrine therapy and knowledge of hormone receptor status in women who were ER or PR positive.

Results:

Not being able to correctly report hormone receptor status was associated with being older and having a lower level of education. Of women who were ER positive or PR positive or both and were at least 40 weeks from diagnosis, having received some form of endocrine therapy was significantly associated with self-identification as being ER or PR positive (OR = 1.82, 95% CI 1.24-2.68, p = 0.002), even when age was taken into account.

Conclusions:

That self-knowledge of hormone receptor status was independently associated with likelihood of receiving endocrine therapy suggests that the methods of helping women understand the nature of their breast cancer are worthy of review.

Introduction

There is evidence that patients who have a good understanding of their disease and who participate in treatment decision making are more likely to better adapt psychologically and possibly physically to their changed circumstances and treatment program.^1
–3 Women with breast cancer generally appear to have a strong desire to be involved in making decisions about their treatment, but there is little information as to whether women actually have the knowledge to make informed treatment choices. In European countries, older women and women who are less educated have been found to be less likely to report receiving information or being involved in their breast cancer treatment decision making.⁴ Findings from a study of American women with breast cancer indicate that the majority of women lack sufficient knowledge about survival and recurrence rates to make informed decisions about surgery.⁵

In recent years, there have been increasing global efforts to ensure that women with breast cancer are provided with the necessary information to actively participate in treatment planning.⁶ In Australia, the National Breast Cancer Center provides resources in both electronic and print media for women.⁷ In addition, an information and resource kit was developed by the Breast Cancer Network of Australia and launched in 2004⁸ and is available at no cost to all women newly diagnosed with breast cancer.

The objective of this study was to determine the level of understanding of women with newly diagnosed breast cancer of their hormone receptor status, one of the key clinical features of their disease that would be important in determining treatment decision making. We also report on the relationship between knowledge of hormone receptor status and the likelihood of a woman being treated with adjuvant endocrine therapy.

Materials and Methods

Study participants

The longitudinal Medical Benefits Fund of Australia Limited Foundation Health and Wellbeing After Breast Cancer Study (MBF Study) was designed to document the physical, psychological, and socioeconomic consequences of breast cancer among women living in Victoria recruited within the first year of their diagnosis and then followed annually for 5 years. Women resident in Victoria who had a histological diagnosis of invasive breast cancer diagnosed between July 2004 and December 2006 and were able to complete the study enrollment questionnaire (EQ) within 12 months of their initial diagnosis were invited to participate in this study. As the women were recruited over a 2½-year period and will each be followed for 5 years, they will complete their final follow-up questionnaires between June 2009 and December 2011. Recruitment to this study has been described in detail elsewhere.⁹ In brief, women were recruited either via a public awareness campaign or by direct written invitation from the Victorian Cancer Registry (VCR). Recruitment via the VCR involved letters of invitation issued directly to women with newly notified invasive breast cancer. It is a statutory requirement that bodies, such as hospitals, pathology laboratories, and BreastScreen Victoria, notify the VCR of new cases of breast cancer. The definitive diagnostic information is obtained from the pathology report, which may be of a surgical specimen or a core biopsy specimen.

Women were excluded if their primary diagnosis of breast cancer was outside the recruitment dates, if they did not have a confirmed histological diagnosis of invasive breast cancer, if the VCR was advised by their treating physician that it would be inappropriate to contact a particular woman because of her physical, psychological, or social circumstances, or finally, if the woman was not able to complete the questionnaire in English. In all, 2135 women agreed to participate, and of these, 1684 women were eligible and completed the baseline EQ. Only 16% of the women contacted through the VCR (by a letter of invitation and phone follow-up) actively refused participation.

Enrolment questionnaire (EQ)

This questionnaire comprised questions about past general medical, gynecological, and family history, lifestyle issues, and past and present prescription and nonprescription drug use. Women were also asked if their tumor was estrogen receptor (ER) or progesterone receptor (PR) positive and if they had received or were still receiving a range of endocrine therapies, including removal of the ovaries, and the use of a range of drugs, including goserilin, tamoxifen, anastrozole, letrozole, and exemestane. For questions about their tumor, the women were given the option to report “don't know.” The questionnaire is a written questionnaire that is mailed to participants with a reply-paid envelope. If a participant has any difficulty completing the questionnaire, she can ring a free-call telephone number for assistance.

Pathology report data

The VCR provided histological confirmation of invasive breast cancer for each participant as well as information about whether the tumor was ER and PR positive. The VCR reports that a tumor is hormone (estrogen or progesterone) receptor positive if ≥1% of the nuclei stain at any level of intensity (low, intermediate, or high).¹⁰ The consolidation rule also applies, which is that if either the diagnostic or treatment specimen tests positive, the tumor is reported as positive. Women's residential postcodes were classified into two groups (metropolitan Melbourne and other) by the Roy-Morgan-Research classification.¹¹

Data analysis

For analysis, “don't know” responses on the EQ were treated as missing data. For analysis of characteristics of the women related to correctly reporting hormone receptor status, both positive and negative, we examined age, level of education, and location of residence within/beyond the Melbourne metropolitan area. Inability to correctly report hormone receptor status was analyzed using multivariate logistic regression with explanatory variables: age (continuous), location of residence (Metropolitan Melbourne or other), and highest level of education attained (none/primary, lower secondary, upper secondary, vocational, bachelor's degree, postgraduate). In this analysis, the two categories in the dependent variable for the logistic regression analysis were (0) women who correctly knew their status (either because they reported they were positive for at least one of the receptors and they were or they reported they were negative for both receptors and were negative for both) and (1) women who reported they did not know their receptor status or did not answer the question.

A second logistic regression analysis used treatment with adjuvant endocrine therapy as the dependent variable and self-report of being hormone receptor positive and age as the explanatory variables.

For this analysis, treatment with adjuvant endocrine therapy was self-reported. In the questions covering treatment of the breast cancer, there is a specific section for endocrine therapies that includes removal of the ovaries and the relevant drugs, which are listed by both their trade and generic names. There is also another section at the end of the questionnaire for women to report any medications they have not listed elsewhere. If one of the relevant drugs was only listed in this section, it was included in the woman's response. All analyses were carried out using SPSS version 16.0 (SPSS Inc., Chicago, IL).

The MBF Foundation Health and Wellbeing After Breast Cancer Study was approved by the Human Research Ethics Committee of the Cancer Council of Victoria, allowing for the exchange of individual-level patient data between the VCR and our study, and the Standing Committee on Ethics in Research involving Humans of Monash University. Written consent was obtained from all participants.

Results

The mean age of the 1684 participants was 57 years (range 26–88 years) (Table 1). The mean time between diagnosis of breast cancer and completion of the EQ was 41 weeks, with 5% of questionnaires completed within 8 weeks of diagnosis and 95% of questionnaires completed within 58 weeks of diagnosis. As previously reported, the age and tumor size distribution of the study participants was consistent with those of Victorian women recently diagnosed with breast cancer.⁹ The participants were predominantly Australian born and urban dwelling but split fairly evenly for working outside the home and for education beyond secondary school (Table 1).

Table 1.

Participant Characteristics

Characteristic	n (%)
Age, years
<40	103 (6.1)
40–59	914 (54.3)
60–79	610 (36.2)
≥80	57 (3.4)
Country of birth^a
Australia	1281 (76.1)
Great Britain	150 (8.9)
Other	233 (13.8)
Data missing	20 (1.2)
Employment: Hours worked outside the home
None	762 (45.2)
<20 hours/week	176 (10.5)
≥20–<40 hours/week	448 (26.6)
≥40 hours/week	298 (17.7)
Education
No formal education/primary	53 (3.1)
Lower secondary	503 (29.9)
Completed secondary (year 12)	363 (21.5)
Vocational	376 (22.3)
Bachelor's degree	178 (10.6)
Postgraduate	208 (12.4)
Unknown	3 (0.2)
Location of residence
Melbourne Metropolitan area	1149 (68.2)
Non-Melbourne metropolitan area	535 (31.8)
Hormone receptor status^b
Both ER^c and PR positive	1050 (62.4)
ER positive only	237 (14.1)
PR positive only	21 (1.2)
Neither ER nor PR positive	258 (15.3)
Not done, result unknown, result unavailable	118 (7.0)

7 women identified themselves as Aboriginal or Torres Strait Islander.

Victorian Cancer Registry data at the time of diagnosis.

ER, estrogen receptor; PR, progesterone receptor.

Knowledge of hormone receptor status

Women's VCR-reported hormone receptor status (by histology) is given in Table 1. Of the 846 women who reported their breast cancer was positive for one or both receptors, 93% (n = 787) were hormone receptor positive at diagnosis (Table 2). However, 791 (47%) women reported they did not know their receptor status or left that field blank, and of these, 65% (511) had positive staining for one or both hormone receptors.

Table 2.

Victorian Cancer Registry (VCR) Data and Participants' Knowledge of Their Breast Cancer Hormone Receptor Status

	ER and PR ^a status according to VCR
Women's self-reported hormone receptor status ^b	ER+ PR+	ER+ PR−	ER− PR+	ER− PR−	Done but unavailable	Not done or unknown	Total
ER+ and/or PR+	639	137^c	11^d	6	36	17	846
ER− PR−	4	2	0	30	2	2	40
Unknown or not reported	406	95^e	10^f	221^g	44	15	791

ER, estrogen receptor; PR, progesterone receptor.

7 women not included whose responses could not be classified.

Includes 2 women who were PR equivocal.

Includes 1 woman ER equivocal.

Includes 3 women PR equivocal and 1 woman PR not done/unknown.

Includes 1 woman ER equivocal and 1 woman ER not done/unknown.

Includes 1 woman PR done not available and 1 woman PR not done/unknown.

Inability to correctly report hormone receptor status was positively associated with both older age (odds ratio [OR] per year 1.037, 95% CI 1.027-1.047, p < 0.001) and lower levels of completed education (compared with a reference of completed postgraduate) (none or primary education: OR 4.9, 95% CI 2.3-10.5, p < 0.001; lower secondary: OR 2.5, 95% CI 1.7-3.6, p < 0.001; upper secondary: OR 3.0, 95% CI 2.1-4.4, p < 0.001; vocational: OR 1.7, 95% CI 1.1-2.5, p = 0.01; bachelor's degree: OR 1.7, 95% CI 1.1-2.6, p = 0.02). In contrast, place of residence was not associated with the presence/absence of correct knowledge (nonmetropolitan vs. metropolitan: OR 1.2, 95% CI 0.9-1.5, p = 0.22) (Table 3).

Table 3.

Univariate and Multivariate Logistic Regression Analysis of Inability to Correctly Report Hormone Receptor Status

	Univariate OR (95% CI)	p value	Multivariate^a OR (95% CI)	p value
Age at diagnosis^b	1.044 (1.034-1.053)	<0.001	1.037 (1.027-1.047)	<0.001
No formal education or primary school^c	9.3 (4.4-19.5)	<0.001	4.9 (2.3-10.5)	<0.001
Lower secondary school^c	3.3 (2.3-4.8)	<0.001	2.5 (1.7-3.6)	<0.001
Upper secondary school^c	3.3 (2.3-4.8)	<0.001	3.0 (2.1-4.4)	<0.001
Vocational education^c	1.9 (1.3-2.8)	0.001	1.7 (1.1-2.5)	0.01
Bachelor's degree^c	1.5 (1.0-2.4)	0.053	1.7 (1.1-2.6)	0.02
Nonmetropolitan vs. metropolitan location of residence	1.3 (1.1-1.7)	0.006	1.2 (0.9-1.5)	0.22

The multivariate analysis includes all variables listed in the table.

OR for age is the ratio of the odds comparing people who differ by 1 year of age.

All education categories compared with the reference category of completed postgraduate.

Of the 1308 women who were ER positive or PR positive or both, 883 were at least 40 weeks from the date of their diagnosis when they completed their EQ and, thus, likely to have completed their initial treatment, which may have included a combination of surgery, radiotherapy, and chemotherapy. It was considered that by this stage they would have been commenced on endocrine therapy if this was to be offered. At this time, the available endocrine therapies included surgical or chemical oophorectomy, tamoxifen, anastrazole, letrozole, and exemestane. Among these 883 women, 738 had received some form of endocrine therapy that was ongoing or they had started some form of endocrine therapy that had subsequently been ceased by the time they completed the questionnaire. Women who received some form of endocrine therapy were, on average, younger than women who had not received endocrine therapy (mean 58.8, standard deviation [SD] 12.0 vs. 61.5, SD 10.7 years, p = 0.01). Women who correctly identified themselves as either ER or PR positive (or both) were more likely to have received endocrine therapy (431 of 491, 87.8%) than women who did not report they were either ER or PR positive (or both) (307 of 392, 78.3%) (p < 0.001). Age (OR = 0.99, 95% CI 0.97-1.01, p = 0.22) and education (see individual categories in Table 4) were not related to having received some form of endocrine therapy if knowledge of hormone receptor status was taken into account, although knowledge of hormone receptor status had a highly significant association with receipt of endocrine therapy in this multivariate analysis (OR = 1.8, 95% CI 1.2-2.7, p = 0.003) (Table 4).

Table 4.

Univariate and Multivariate Logistic Regression Analysis of Having Received Endocrine Therapy, Restricted to Women at Least 40 Weeks from Time of Diagnosis

	Univariate OR (95% CI)	p value	Multivariate ^a OR (95% CI)	p value
Age at diagnosis^b	0.98 (0.97-0.99)	0.012	0.99 (0.97-1.01)	0.22
No formal education or primary school^c	0.7 (0.2-2.1)	0.54	1.1 (0.4-3.4)	0.82
Lower secondary school^c	0.7 (0.3-1.3)	0.23	0.8 (0.4-1.6)	0.61
Upper secondary school^c	0.7 (0.3-1.3)	0.24	0.8 (0.4-1.6)	0.50
Vocational education^c	0.8 (0.4-1.6)	0.47	0.8 (0.4-1.7)	0.63
Bachelor's degree^a	0.9 (0.4-2.4)	0.92	0.9 (0.4-2.4)	0.93
Correct knowledge of being ER or PR positive	2.00 (1.4-2.9)	<0.001	1.8 (1.2-2.7)	0.003

The multivariate analysis includes all variables listed in the table.

OR for age is the ratio of the odds comparing people who differ by 1 year of age.

All education categories compared with the reference category of completed postgraduate.

Discussion

This study of the level of knowledge of hormone receptor status in a large community-based cohort of Victorian women with newly diagnosed invasive breast cancer indicated that many women could not report their hormone receptor status. Inability to correctly report hormone receptor status was associated with being older and having a lower level of education. Among women who were hormone receptor positive, being aware of being hormone receptor positive was independently associated with the likelihood of receiving endocrine therapy.

Previous studies have reported on the understanding of women with breast cancer of the terminology related to this condition,¹² their understanding of recurrence and survival,⁵ and their receipt of information and perceived participation in decision making.⁴ This is the first study to explore the capacity of women with breast cancer to report on hormone receptor status, one of the disease parameters considered most important in treatment planning and how patient self-reporting compared with individual pathology report-level data.

Use of adjuvant endocrine therapy in hormonally responsive breast cancers is considered the gold standard of care. Such therapies have been shown to reduce the likelihood of recurrence by about one third.^13
–15 Thus, considering the therapeutic significance of hormone receptor status, the deficit in knowledge pertaining to ER and PR status, with about one half of women unable to provide information about hormone receptor status, is of concern.

Our findings show that older and less educated women were less able to report details about their breast cancer, which is consistent with previous studies in other populations.^4,12 Our findings do not provide evidence that these women were less likely to have been informed nor that they were informed and did not retain the information. However, it indicates that communication of information to women about their breast cancer in a way that positively influences ongoing interactions with their healthcare providers needs to be further addressed.

The extent of the lack of knowledge exhibited by our study population was greater than anticipated, in that recruitment to this study took place after a national effort by both the National Breast Cancer Centre and the Breast Cancer Network of Australia to provide support materials for women with breast cancer^7,8 and continued during a period of heightened community awareness of breast cancer treatment options. The latter included media coverage surrounding the approval of aromatase inhibitor therapy as first-line adjuvant endocrine treatment and an extended public debate over the funding of trastuzumab.

The information on the use of endocrine therapies in this study was self-reported and could not be validated against medical records, as the women live in urban, rural, and remote locations and are receiving their clinical care from a large number of different healthcare providers in both the public and private healthcare sectors. However, limiting a study such as this to large clinics in which self-reported information could be validated would also likely provide an idealized picture of the nature of breast cancer care. We accept that the there are problems with the self-reporting of oophorectomy, with women tending to underreport the procedure.¹⁶ Because in this study women were asked about recent oophorectomy in the context of their treatment for breast cancer, however, we consider that their reporting of the procedure may be more accurate than it is in the context of routine questioning.

The fact that knowledge of hormone receptor status was independently associated with the likelihood of a woman reporting that she had received or was still receiving endocrine therapy could be explained by the fact that women who know they have had some form of endocrine therapy are more likely to recall that they are hormone receptor positive. Alternatively, women who know their hormone receptor status may have been more likely to have participated in the decision making about using endocrine therapy. If the second explanation is the case, the consequences of the level of a woman's understanding of her disease are not trivial and are associated with her therapy. Seeing the woman as an advocate for her own therapy should encourage both women and their clinicians to give understanding and retention of information about the disease the priority it deserves.

In conclusion, we report that despite a concerted national effort to ensure that women with newly diagnosed breast cancer have the information to enable them to be actively involved in their treatment plan, many women, particularly less educated and older women, appear to lack fundamental knowledge of their disease. That knowledge of hormone receptor status was independently associated with the likelihood of a woman reporting endocrine therapy highlights that women's understanding of their disease may have tangible consequences.

Footnotes

Acknowledgments

This study was funded by the MBF Foundation, the National Health and Medical Research Council of Australia (grant No. 219279), Novartis Oncology Australia, the L.E.W. Carty Trust, the Jack and Robert Smorgon Families Foundation, Connie and Craig Kimberley, and Roy-Morgan-Research.

We thank the study participants and the members of our Study Advisory Group: Dr Jacquie Chirgwin, Assoc. Professor John Collins, Professor Graham Giles, Mr. Peter Gregory, Mr. Stewart Hart, Miss Suzanne Neil, Ms. Onella Stagoll, and Mrs. Avis McPhee.

We thank Melisa Bagnato and Julie de Crespigny from The Cancer Council Victoria for their contribution to recruitment. We also thank Breast Cancer Network Australia for their review of the study questionnaire. Finally, we thank Professor Graham Giles, Director of the Victorian Cancer Registry, for his ongoing support of this study.

Disclosure Statement

The authors have no conflicts of interest to report.

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