Understanding breast cancer responsiveness

Dr. Karen Gelmon (biography and disclosures)

What I did before

When I started treating breast cancer, systemic therapy recommendations were usually based only on the menopausal status of the woman and whether there was cancer in the axillary nodes.  Although estrogen status was being measured the importance of this marker was not appreciated.

What changed my practice

In the last decade there has been an explosion of information about the genetics and molecular makeup of breast cancers with a heightened understanding that breast cancer is not one disease. A landmark publication in 2000 described four types of breast cancer. ¹ In a recent as yet unpublished study using newer sequencing technology, researchers at the BC Cancer Agency and collaborators from the UK have suggested 9 distinctive types of the disease. ²  The recognition of these subtypes of breast cancer is changing how we approach and treat the disease.

The risk of recurrence is a major concern when an early breast cancer is diagnosed as even with excellent surgery there is a risk of both local and systemic recurrence.  Architectural factors such as the size of the tumour and nodal involvement have classically been used to determine risk. Biological features such as estrogen receptor status, HER2 expression and grade, often measured by Ki67, are now being included in our risk assessment.

The responsiveness of the tumour has also become an important determinant in how we treat the disease.  Responsiveness describes how the tumour will be affected by specific treatments.   For example, estrogen receptor status determines whether a breast cancer will respond to endocrine therapy; the gene HER2 is associated with response to anti HER2 therapy such as trastuzumab (Herceptin); and high KI67 tumours may be more responsive to chemotherapy than those with a lower grade or KI67.  Thus two similar sized tumours may get different treatment recommendations based on their biology.

What I do now

For patients with low grade estrogen receptor positive tumours I am recommending much less chemotherapy even if there is nodal involvement and/or the woman is premenopausal.  In these tumours, endocrine therapy may be the most effective treatment and chemotherapy may minimally impact survival.  Having said that, some patients still benefit from including chemotherapy in addition to hormone therapy.  For patients with HER2 overexpressing tumours I often recommend chemotherapy and trastuzumab even if the tumour is small with no involved nodes.  Understanding the biology of breast cancers is providing more personalized recommendations and this is translating into better outcomes.

As we further define subtypes, more targeted treatments will be developed but at this time for many cancers we continue to give broad cytotoxic therapy.  As well, new agents are being developed and may be further decrease recurrences. We are also now frequently rebiopsying recurrent cancers to further understand the markers of response and resistance and to tailor treatment. We also need to study the “host” patient, as the pharmacogenomics of the individual may affect how the drug is metabolized and also may contribute to the effectiveness and the toxicity of the therapy.

How does this affect family physicians?  Treatment recommendations may be more complicated so counseling patients prior to their oncological consultation may be more confusing.  It may be more difficult to know whether chemotherapy will be recommended or not especially if we begin to do more complex assessments of tumours in specialized laboratories. Numerous studies are reported in the lay and academic press and are never substantiated.  Understanding what is of relevance to the care and management of our patients and which data is transient is difficult.  We need to ensure that the government prioritizes an upgrade of our electronic BC Cancer Agency website and electronic record to make it accessible to primary health care providers with the appropriate, evidence based results.

Biological information is often available as soon as the core biopsy diagnoses an invasive cancer.  Early referral to centres with multidisciplinary teams may avoid long delays and confusing information for both the patient and the primary care providers.  Electronic integrated systems may also aid the transfer of information. Frequent updates at family practice meetings and in journals can also provide current treatment and care models to a wider audience.  With this knowledge, family practices can provide a broad idea of the concept of adjuvant therapy for the treatment of early breast cancer and introduce the idea of chemotherapy, hormones and radiation without specifying the details.  Family doctors should be aware of the new patient package, including a patient book that is available through the Alliance for Breast Cancer Information at the BC Cancer Agency. ³ Reassuring patients about the improvements in survival as over 90% of early breast cancer cases in BC now live over 5 years will also help provide helpful information to decrease a woman’s anxiety. 4

References (Note: Article requests require a login ID with CPSBC or UBC)

1. Perou CM, Sorlie T, Eisen MB, et al.  Molecular portraits of human breast tumours.  Nature 2000; 406 (6797): 747-52 (View article with CPSBC or UBC)
2. Personal communication with Dr Samuel Aparicio
3. Alliance for Breast Cancer Information BC, 604 707 5818, and Intelligent Patient Guide – Olivotto, Gelmon, McCready, 5^th edition, 2011 (book)
4. Coleman MP, Forman D, Bryant H et all.  Cancer survival in Australia, Canada, Denmark, Norway, Sweden and the UK, 1995-2007 (the international cancer benchmarking partnership): an analysis of population –based cancer registry data.  Lancet 2011; 377(9760): 127-138. (View article with CPSBC or UBC)

Cancer Care Outreach Program on Education (CCOPE)

Over the past 4 months, UBC CPD in partnership with BCCA and FPON has been delivering case-based workshops on breast cancer care to various communities in BC, the last workshop is scheduled for Dawson Creek on March 28^th.  Workshop contents covers screening guidelines, diagnostic procedures, main treatment options and their potential side effects, and follow-up of breast cancer patients.

Read more about the Cancer Care Outreach Program on Education (CCOPE) .

Read more about CCOPE – Breast Cancer Community Workshops.

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Understanding breast cancer responsiveness

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