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Enhancing treatment adherence in advanced breast cancer patients
Despite substantial improvements in its prevention, diagnosis, and treatment, advanced breast cancer (ABC) remains a significant clinical problem. In the USA, although fewer than 10% of women diagnosed with breast cancer present with distant metastases, some 40,000 die annually of the disease. [1] In Europe, 2004 estimates suggest that breast cancer accounts for nearly one fifth (17.4%) of the total number of deaths from all types of cancer among women. [2]

While advances in endocrine treatment have helped to delay disease progression and prolong survival among postmenopausal women with ABC, multiple comorbidities are a common problem and pose important management challenges. Particularly critical is the association between comorbid disease and increased therapy burden, which can lead to suboptimal adherence to oral chemotherapy and limit treatment efficacy. [3,4] Although few studies have adequately explored the role of polypharmacy in treatment adherence in breast cancer patients, evidence suggests that patients’ perception, beliefs, and motivation play an essential role. [4,5]

Polypharmacy and advanced breast cancer
With increasing age, women with ABC are more likely to suffer from comorbid conditions such as hypertension, heart disease, arthritis, and diabetes. [6] Notably, these conditions often require oral therapy, with the result that patients are often burdened with multiple dosing schedules and treatment courses that largely rely on self-medication. This is exemplified by a recent study of 851 postmenopausal women with ABC, in which an overwhelming 81.9% of patients were receiving concomitant oral medications, with 25.3% receiving five or more, and 10.9% seven or more different agents. [7] Not surprisingly, the mean number of oral medications received by study participants increased with age. [7]

Not only is patient adherence of great concern when medications are self-administered, [4] but, poor adherence related to polypharmacy and multiple daily dosing schedules can also be problematic. For example, a systematic review of association between dose regimens and medication adherence based on electronic monitoring rather than patient self-reporting demonstrated an inverse relationship between the prescribed number of daily doses and adherence across a range of therapeutic classes of drugs. [8] Poor compliance due to polypharmacy has also been demonstrated in Type 2 diabetes. [9] Hence, it is possible that adherence may also be compromised among women with comorbidities who are receiving oral anti-cancer therapies.

While there is still much to be learned about the multitude of factors that contribute to treatment efficacy in ABC, suboptimal adherence may prove to be one of the greatest barriers to effective use of new oral anti-cancer agents, [3] and an important reason for therapy failure. Although one school of thought suggests that the seriousness of a patient’s illness provides adequate motivation for treatment adherence, [4] this has not been borne out in clinical studies of cancer and other chronic diseases. In fact, results of a recent meta-analysis demonstrate that patient adherence to orally administered anticancer therapy is variable, unpredictable, and may be as low as 20% or less. [3] Hence, gaining a better understanding of patient preferences and the issues surrounding intentional or unintentional non-adherence, and discussing the importance of adherence with patients, is essential.

Concordance and patient preference
Education is only one key component of the clinician-patient interaction, and successful disease management may ultimately rely upon concordance, i.e. shared decision-making between the clinician and patient. [10] Even among patients with chronic diseases, the concepts of risk and benefits of adherence can be difficult to fully comprehend, particularly when the treatment course is long term and requires a complex dosing schedule.

It is generally believed that given the choice, most patients will choose the least invasive form of therapy, such as oral treatment rather than injection. However, there are no systematic data to support this view. Preliminary findings of an observational study of 208 women with breast cancer exploring preference for different routes of administration of treatments demonstrated that nearly 25% would prefer a monthly injection to a daily tablet, with 12% expressing no preference. [5] Notably, among the women who expressed a preference for injections, 43% stated that it was to ensure adherence, while nearly 49% of patients currently receiving oral medications admitted to forgetting to take their tablets on more than one or two occasions each week. [5] Furthermore, after consideration of different scenarios, patients significantly altered their preferences, with most (61%) stating that they would prefer an injection if it was associated with fewer hot flashes, and an even larger majority (74%) preferring an injection if it offered an improvement in efficacy over oral therapy. [5]

As convenience is a major factor in treatment choice, injections may represent the first choice for many patients, particularly among women already treated by the parenteral route. In the previously cited study examining the incidence of polypharmacy among breast cancer patients, almost 20% were already being treated by the parenteral route. [7] Therefore, it is possible that some of these patients may find it convenient to receive their anti-cancer therapy at the same time.

Choosing the right route
In the endocrine treatment of ABC in postmenopausal women, available agents may have similar efficacy and tolerability profiles but different routes of administration. While tamoxifen and the newer, third-generation aromatase inhibitor anastrozole are given orally, the estrogen receptor antagonist fulvestrant is administered by intramuscular injection once a month. Notably, fulvestrant has been shown to be at least as effective as anastrazole in terms of median time to progression, [11] objective tumor response, [12] and duration of response, [11] and due to its mode and frequency of administration, may offer certain advantages for patients with hormone-sensitive breast cancer. Indeed, a monthly injection may be preferable to some patients, not only in terms of offering a convenient dosing schedule that allows patients to remain mindful of their disease without it interfering with daily living or other treatment regimens, but also by providing an opportunity for patient support and counseling while promoting treatment adherence.

Communication is key
Data suggest that patient perceptions, beliefs, motivations, and preferences have important implications for treatment adherence. Acknowledging and addressing these factors in a concordant fashion can help clinicians ensure that adherence is achieved, particularly among patients who are likely to find the challenges of polypharmacy burdensome.

  1. Siebel MF, Muss HB. The influence of aging on the early detection, diagnosis, and treatment of breast cancer. Curr Oncol Rep 2005; 7: 23-30.
  2. Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol 2004; 16: 481-88.
  3. Partridge AH, Avorn J, Wang PS, Winer EP. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst 2002; 94: 652-61.
  4. McLeod HL, Evans WE. Oral cancer chemotherapy: the promise and the pitfalls. Clin Cancer Res 1999; 5: 2669-71.
  5. Fallowfield L, Atkins L, Morris R, Price M, Langridge C, Cox A et al. Routes of administration in breast cancer: preliminary findings from a patient survey. Presented at Primary Therapy of Early Breast Cancer 9th International Conference. St. Gallen, Switzerland; 26-29 January 2005.
  6. Nagel G, Wedding U, Hoyer H, Röhrig B, Katenkamp D. The impact of comorbidity on the survival of postmenopausal women with breast cancer. J Cancer Res Clin Oncol 2004; 130: 663-70.
  7. Robertson JFR. Incidence of polypharmacy in patients with breast cancer. Presented at Primary Therapy of Early Breast Cancer 9th International Conference. St. Gallen, Switzerland; 26-29 January 2005.
  8. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296-310.
  9. Penformis A. Drug compliance in type 2 diabetes: role of drug treatment regimens and consequences on their benefits. Diabetes Metab 2003; 29: S31-7.
  10. Jones G. Prescribing and taking medications. BMJ 2003; 327: 819.
  11. Robertson JFR, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women. A prospective combined analysis of two multicenter trials. Cancer 2003; 98: 229-38.
  12. Mauriac L, Pippen JE, Albano JQ, Gertler SZ, Osborne CK. Fulvestrant (Faslodex™) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. Eur J Cancer 2003; 39: 1228-33.


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