Thursday, January 10, 2013

Unanswered questions

I've been reflecting on the fact that for so many of the common clinical situations I face every week as a breast cancer oncologist, I don't have the answers. Despite great advances in understanding the biology of breast cancer and refining of the diagnostics and therapeutics, there are so many questions that come up in everyday practice that leave me in and my colleagues in the dark:
Which ER positive, node negative patients really need chemo in addition to hormonal therapy?  
How do you predict in advance which patients are going to develop dose-limiting toxicity from breast cancer treatment, like intractable joint symptoms from AI's or neuropathy from Taxol? 
What's the final word on CYP2D6 and tamoxifen? 
How do I help patients lose the weight they gained during adjuvant chemo or hormonal therapy? 
Who should get an MRI or US in addition to mammogram?
What's the best sequence of hormonal therapy for postmenopausal women with metastatic breast cancer?
Is there harm in delaying the start of adjuvant chemotherapy following definitive local therapy more than 4-6 weeks?
Should you give adjuvant trastuzumab to women with HER2 positive cancers less than 1 cm?
Is more than five years of an aromatase inhibitor better than 5 years in the adjuvant setting? 
Is a negative margin following lumpectomy defined as 2 mm, 1 mm, or just no tumor at ink?
Should you do an Oncotype for every healthy patient with an ER positive, node negative tumor between 5 and 10 mm in size or just some?
What's the role for local therapy of the primary tumor in the asymptomatic patient with metastatic disease?
What's the best systemic management for metaplastic carcinoma? 

This list could be endless. These are extremely common scenarios every oncologist who treats breast cancer sees over and over, and we don't know the "right" answer to any one of them. We have some ideas for most of them, and we certainly have plenty of clues as to how to try to figure out many. For some, it's easy to envision that clinical trials may eventually provide an answer, such as the optimal duration of AI's or the management of small HER2 positive tumors, but it will take years. Some of these may become less relevant as technology advances. For example, as we develop more sophisticated imaging, the current dilemmas about false positives with MRI will likely fade. As we develop better predictive markers than Oncotype and Mammaprint (or at least when we learn how to use those two optimally), adjuvant chemotherapy decisions will become much less ambiguous. As we start to understand predictors of toxicity such as which SNPs predispose patients to neuropathy (and we already have some good information for that one), we can be more selective about which patients we expose to drugs like taxanes.

But until then, every week in my clinic, I have to tell my patients that I don't really have answers to these questions. And as distressing as it can be for me as a healthcare professional to constantly repeat the "We don't know" refrain, it is far more than that for the patient and family who are on the receiving end of my non-answer. It is annoying, disconcerting, frightening, frustrating, and maddening, at many levels. And probably quite a few more emotions than that. 


  1. And you can add:

    Will the addition of breast radiation or tamoxifen to lumpectomy change the likelihood of dying of breast cancer for the patient diagnosed with ductal carcinoma in situ?

  2. Bob - this is a great post and I'll stress that it's just as frustrating for physicians as it is for patients to not have all the answers. We are making progress but it is very slow, especially for those with metastatic disease.

  3. If everything on the list above and an extended version were known, we wouldn't have a problem, and you'd have no job security but, it would be a much happier world for many. D