In clinical research, chart review is nearly as familiar as daily functions like walking or breathing. My days are full of identifying missing variables, finding them in the electronic medical records, then documenting them in my meticulously organized data sheets. However, during these chart reviews, my mind tries to find a way to break out of autopilot by looking for trends in the data. That’s how I recently noticed the frequency of the letter “L.”
In the field of breast cancer, breasts often (not always!) come in pairs, and unsurprisingly, knowing where the cancer is located is an imperative factor for management. For my data sheets, I prefer to keep things simple with an “L” for left and an “R” for right. Not long ago, as I was reaching the 1,000th patient chart review, I noticed that “L” seemed to show up more often. I had assumed that this was something I had made up. But upon summing up left vs. right cases, it was true—left was notably more common!
Naturally, I went straight to PubMed to do a quick literature review and found an article titled “Laterality of Breast Cancer in the United States,” published in 1996 in the journal Cancer Causes and Control. This study evaluated over 250,000 cases of breast cancer to determine differences between left vs. right breast cancer. What was discovered was that for both invasive and in situ (non-invasive, early-stage) breast cancers, there was a statistically significant trend of the left breast being more involved than the right. In fact, out of 234,657 cases of invasive breast cancer, there were 6,105 more cases of left-sided breast cancer than right. Similarly, out of 21,031 cases of in situ breast cancer, there were 593 more cases of left-sided breast cancer than right.
As to why the left breast has a higher frequency of breast cancer than the right, the evidence is still inconclusive. The 1996 study mentions that the left breast does tend to be larger than the right, but it is unclear whether breast size alone would account for the difference in cancer rates based on laterality. Possibly, there is a difference in the biology between the left and right breasts. Dr. Ramsdell is one of the researchers trying to elucidate these differences, as discussed in a 2015 TEDx Talk. The research shows that in MMTV-cNeuTg/Tg mice, mammary glands display left vs. right differences in susceptibility to HER2/Neu, a protein involved in breast cancer growth. This finding suggests that there may be a genetic component at play causing the left vs. right differences we observe in breast cancer.
What do we do with this information? In general, the field of breast oncology does not hinge much of its approach to screening, diagnostics, or therapies on breast cancer laterality. Although there is ongoing research, such as that conducted by Dr. Ramsdell, to identify the mechanism underlying breast cancer laterality, the exact cause is still largely unknown, limiting the clinical utility of this phenomenon in practice. Additionally, although the difference between left and right breast cancer frequency is statistically significant in the 1996 study, the frequencies are not so dramatic that they would alter day-to-day clinical practice in breast oncology. It is also important to understand that these findings in no way suggest giving preferential medical attention to one side; appropriate and attentive health management should take place in equal measures regardless of laterality.
So, it seems that for now, differences in breast cancer based on laterality remain an interesting observation that deserves further investigation, yet with unclear applicability to health care. However, we ought to remain curious about the biological underpinnings revealed through laterality asymmetry. What other tissues and organ systems are impacted by laterality?
Thomas Amburn is a general surgery resident.
