I knew for decades that I had one primary genetic relative who was diagnosed with breast cancer at the age of 41. Beyond that, my genetic family history was unavailable to me. When I underwent my first screening mammogram at the same age, it was more of an inconvenience than a source of worry. Even when I was called back for a follow-up, “clarification” diagnostic mammogram, I had no sense of worry at the time, because breast cancer prevention recommendations seemed ever-changing and often annoyingly conflicting. The sense of urgency and importance of being proactive escaped me. I might have been one of the ultimate stakeholders in that debate, but it seemed like an endless exercise to sort out the specifics on how that debate applied to me.
Inconsistent medical organization recommendations of the past aside, I knew it was common for mammograms to be inconclusive or even lead to false negatives, while MRIs could lead to false positives, biopsies etc. I also knew that, while East Asian women have lower rates of breast cancer, when breast cancer does occur, it can happen at a younger age and is often more difficult to treat. Additionally, I helplessly witnessed my neighbor with cancer endure and succumb to physical, psychological and financial toxicity as she and her family tried to find options, navigate multiple medical systems and was disqualified from clinical trials mid-treatment.
For me, these and other life experiences added up to this conclusion: I needed a more definitive, honest picture of my personal risk for breast cancer. So in my early 40’s, I sought out sequence-based (germ line) genetic testing. If on the off-chance genetic testing yielded any significant results, those results would clarify my risk much more than an inaccessible family history or repetitious radiology. At the time, I questioned the widespread belief that breast cancer was something that could be caught early, treated and life could go on. Later I learned through the work of Cyrus Ghahar and other researchers (Schmitt-Kittler et al, Pantel et al.) that there was validity to my doubt. The “catching things early” approach was not early enough for my own personal risk tolerance. For me, it seemed that by the time something was visible upon radiology or palpation, the gates to the hell that I watched my neighbor go though could have already been cracked. But if I had more information, it could allow me to opportunity try to proactively outsmart cancer, rather than react to it should it occur.
After getting the phone call from the medical genetics department of the university medical center, the first words out of my mouth were, “Well, I cannot think of a better place to be to receive this news”. I would later learn that PALB2 is a protein that helps BRCA1 connect to BRCA2 when a cell is in the process of dividing. I would also learn that a pathogenic PALB2 mutation is associated with other cancers, some with risk-reducing options and others with reasonable-to-me surveillance options (Norquist et al., Pritchard et al.)
Six months after news of my PALB2 mutation, my breast and ovarian cancer risks were reduced to lower than average levels, lower than for those without known mutations and/or family history. Plans are in place to address any additional cancer risks associated with this gene. While I never felt the need for anyone but my doctors to validate my decisions, a little over a year later, I learned that the source of my mutation died of metastatic breast cancer, almost three decades after initial diagnosis and treatment.
I consider myself incredibly lucky. “Luck” is defined as “opportunity meets preparation”. The opportunity to have germline genetic testing coupled with having solid resources in place was my big lucky break. My “luck” has brought me immeasurable peace of mind for which I am deeply grateful.
Bio: @PALB2Previvor is a former bench researcher and grad school dropout. She now lives in the Pacific Northwest with her partner and dogs. She has been an active FORCE volunteer and advocate since learning of her mutation status.
Grady, D. Panel Reasserts Mammogram Advice That Triggered Breast Cancer Debate. New York Times January 11, 2016
Perry CS, Otero JC, Palmer JL, et al. Risk factors for breast cancer in East Asian women relative to women in the West. Asia–Pacific Journal of Clinical Oncology 2009; 5: 219–231. doi:10.1111/j.1743-7563.2009.01242.x
Schmidt-Kittler O, Ragg T, Daskalakis A, et al. From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. PNAS June 24, 2003 100 (13) 7737-7742; https://doi.org/10.1073/pnas.1331931100 https://www.pnas.org/content/100/13/7737
Pantel K, Müller V, Auer M, et al. Detection and clinical implications of early systemic tumor cell dissemination in breast cancer. Clin Cancer Res. 2003 Dec 15;9(17):6326-34. https://clincancerres.aacrjournals.org/content/9/17/6326
Simhadri S, Vincelli G, Huo Y, et al. PALB2 connects BRCA1 and BRCA2 in the G2/M checkpoint response. Oncogene. 2019;38(10):1585–1596. doi:10.1038/s41388-018-0535-2 https://www.nature.com/articles/s41388-018-0535-2
Norquist BM, Harrell MI, Brady MF, et al. Inherited Mutations in Women With Ovarian Carcinoma. JAMA Oncol. 2016;2(4):482–490. doi:10.1001/jamaoncol.2015.5495 https://jamanetwork.com/journals/jamaoncology/fullarticle/2479125
Pritchard CC et al. N. Engl. J. Med. 2016 Aug;375(5):443-53 https://www.nejm.org/doi/full/10.1056/NEJMoa1603144
Tags: genetic testing, HBOC Week, hereditary cancer, PALB2, previvor, Privivor Day