How Breast Cancer Innovation Paved the Way for Personalized Medicine in Oncology

By Jeff Kimbrough, Head of Strategic Partnerships & Genomics Subject Matter Expert, Reference Medicine

Innovation in cancer research, diagnostics, and tumor profiling has come a long way over the years. Yet more than 42,000 people in the US – and more than 685,000 globally – are still dying from breast cancer each year.¹ About one in eight women will be diagnosed with invasive breast cancer in their lifetime, and despite a similar incidence, mortality from breast cancer among Black women is 41 percent higher compared with White women.¹

We all read these staggering statistics every October when Breast Cancer Awareness Month rolls around. And while the numbers are jarring and there’s still more work to be done, there’s also hope. The overall five-year survival rate for breast cancer in the US is 91 percent, and for localized cancer, it’s 99 percent.²

Because our job at Reference Medicine is to provide oncology samples to researchers who are working on tumor profiling, diagnostics, and other innovations – for breast cancer and all cancers – we want to take the time this Breast Cancer Awareness Month to recognize and celebrate how far the industry has come in tumor profiling and personalized medicine. And we want to reflect on how breast cancer was one of the first areas of oncology to pave the way and lead to breakthroughs for people living with all cancers.

The Promise of Genomic Profiling

Just about everyone knows someone who’s been affected by breast cancer. And as someone with a long career in genomics sequencing, precision medicine, and oncology assay development, I’ve had a lot of people call me over the years and tell me that their sister, mother, friend, etc., has been diagnosed with breast cancer. They ask me, “Is there anything she should do?”, and my response is always the same: “Have they gotten a comprehensive genomic profiling of the tumor?” I cannot understate how important genomic tumor profiling is, or how fortunate we are to live in a time where it’s possible.

Essentially, genomic tumor profiling is a way to personalize cancer treatment. It looks at a sample of the cancer cells for unique gene changes that help the cancer grow and spread.³ Physicians can use this information to determine which treatments are most likely to be effective against that specific cancer type; this type of precision treatment can lead to both reduced side effects and better outcomes.³

Yet despite the benefits of this approach, many women don’t have their tumors profiled. Sometimes it’s a lack of knowledge of what that means or that it’s even an option, sometimes it’s the assumption that because their grandmother died of breast cancer, there’s nothing they can do. And for millions of women around the world, it’s because of a lack of access to such testing and technology. One of the most important things Reference Medicine aims to do is enable the expansion of that access, to make sure tumor profiling – and in turn, personalized treatments – become more widely available.

The Beginning of Biomarker Science – Breast Cancer Sets the Stage

In the past, breast cancer diagnosis, prognosis, and treatment decisions were based on clinical-pathological analysis of the breast cancer tissue and nearby lymph nodes.⁴ Breast cancer was early on classified according to pathologic tumor type, histological grade, and cancer involvement of the lymph node(s) and distant organ(s). ⁴ Forecasts about prognosis and recommendations about treatment would be based on those features, which imperfectly predict clinical outcomes and could result in excessive treatment of many patients with chemotherapy for marginal benefit. ⁴

With the advancement of science, steroid hormone receptors status and later on HER2 status were added to the initial pathologic examination, which vastly improved the selection of patients for therapies based on these biomarkers’ results (positive vs negative).

While we’ve been aware for decades that breast cancer outcomes can vary significantly from one patient to another, gene expression profiling was another step that highlighted these differences at the genetic level. ⁴ Gene microarray analysis, which started gaining attention in the mid-1990s, was built on the idea that only a small portion of our genes at one time and in some cells actually get turned into messenger RNA (mRNA), which then gets translated into proteins. ⁴ These proteins play a crucial role in defining how these cells behave. ⁴ With gene microarray techniques, scientists can now compare the expression of thousands of genes all at once, helping them create detailed profiles for different types of breast cancer.⁴

The next step in improved technology came in the mid-2000’s when Next-generation sequencing (NGS) emerged, revolutionizing the field of genomics and molecular biology further. Unlike traditional Sanger sequencing, which was slow and costly, NGS allows for massively parallel sequencing, enabling the simultaneous sequencing of millions of DNA or RNA fragments. This advancement greatly accelerated research by providing faster, more affordable, and highly accurate genome analysis.

Since the adoption of NGS in breast cancer research and clinical diagnostics, comprehensive analysis of key genetic mutations, such as BRCA1, BRCA2, and PIK3CA, that drive breast cancer progression are incorporated in routine standard of care or even for hereditary screening for family members of those who have been diagnosed. NGS provides detailed insights into the tumor's genetic landscape, helping to identify not only somatic mutations that occur within the tumor itself, but also the inherited risks that an individual may have been born with.⁹

This broad genomic profiling has deepened our understanding of how diverse breast cancer can be. ⁴ It has challenged the way we classify breast cancer, provided valuable insights into prognosis, and, most importantly, started to shape treatment options, especially for people with early-stage breast cancer. ⁴

Applying the Lessons Learned – Precise Tumor Information Leads to Precision Medicine

The scientific innovations we’ve seen in the breast cancer space are now expanded to nearly all cancer types; we’re now able to take the data and information gleaned from genomic tumor profiling and translate that information into new, more precise and genomically targeted therapies to battle cancer, which has been shown to significantly increase survival. Oncologists have shifted from looking at a cancer based on the organ it is in, but towards the genomic variants and other biological differences that are driving the growth of that tumor.

Think about the patient journey, from diagnostics to tumor profiling to treatment. Mammograms are still one of the most important tools at our disposal to help screen for and diagnose breast cancer and are often the best way to detect breast cancer early, when it’s most treatable.⁵ If there are unusual/suspicious findings on a mammogram, the next step is a small breast biopsy – such as a fine-needle aspiration biopsy or core needle biopsy – which can determine whether the area in question is malignant or benign.⁶

Where genomic profiling plays a role, then, is not in diagnosis, but in understanding more about the specifics of the person’s cancer once it is diagnosed, so that physicians can prescribe treatments that are as specific and personalized – and as likely to succeed – as possible.

Precision medicine, in breast cancer and other cancers as well, helps care teams understand how an individual may to respond to certain medications, helps predict whether a certain medication is likely to be effective, and helps identify the medications most likely to be effective based on the particular type of cancer cells present.⁷ In summary, precision medicine allows for more personalized and effective medical treatments, as it considers the unique characteristics of each patient’s cancer rather than treating all patients with the same therapy.⁸  It has, by all accounts, revolutionized treatment outcomes.⁸

Of course, none of the benefits of precision medicine can be realized if the people who need it don’t have access to it.

Ensuring Access to Scientific Innovation – For Everyone

The unfortunate reality is that thousands of people are still dying of breast cancer every year around the world, and access to genomic tumor profiling is not nearly as abundant as it should be inside and outside the US.

The odds that a woman outside the US – or even in very rural areas within the US – will end up with the most advanced tumor profiling and precision medicine options, which could be the difference between life and death, still feel like a toss of the dice in many cases.

Imagine a woman in a small town USA, who lives two hours from the nearest major hospital. What are the chances that her general practitioner is caught up on the latest literature and will know that these options exist? And if she does get that needle-in-a-haystack oncologist who spends all their free time reading the latest research, what are the chances that her health insurance will cover these costly tests? What are the odds that the patient has the health literacy levels and the wherewithal to have been performing self-checks so that the cancer was caught early? Or that she’ll be able to secure daycare and take time off from her hourly wage job to afford all the doctor’s appointments? It’s easy to forget that the deck is still stacked against so many women around the world.

But one of the things I love so much about working at Reference Medicine is that it’s our mission – which truly aligns with my personal mission – to change that. It’s our job to provide researchers and diagnostic developers with high-quality tumor samples quickly and affordably so that high-quality cancer care gets within reach of the people who don’t live next to the big hospitals in major academic centers. If we can help startup companies and small labs continue the important work they’re doing – affordably – then we’re playing some small part in getting the innovations to the patients who need them. And that’s no small thing.

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References:

1. “Breast Cancer Facts & Figures.” Stop Breast Cancer, 2024, www.stopbreastcancer.org/information-center/facts-figures. Accessed 16 Oct. 2024.

2. “Breast Cancer Facts & Stats.” National Breast Cancer Foundation, www.nationalbreastcancer.org/breast-cancer-facts. Accessed 16 Oct. 2024.

3. “What is Genomic Testing in Cancer?” WebMD, www.webmd.com/cancer/what-is-genomic-testing. Accessed 16 Oct. 2024.

4. Bao T, Davidson NE. “Gene Expression Profiling of Breast Cancer.” Adv Surg. 2008;42:249-60. doi: 10.1016/j.yasu.2008.03.002.

5. “Mammograms: What You Need to Know.” Breastcancer.org, Breastcancer.org, https://www.breastcancer.org/screening-testing/mammograms. Accessed 16 Oct. 2024.

6. “Breast Biopsy.” Mayo Clinic, Mayo Foundation for Medical Education and Research, https://www.mayoclinic.org/tests-procedures/breast-biopsy/about/pac-20384812. Accessed 16 Oct. 2024.

7. “Precision Medicine for Breast Cancer.” Mayo Clinic, Mayo Foundation for Medical Education and Research, https://www.mayoclinic.org/tests-procedures/precision-medicine-breast-cancer/about/pac-20522213. Accessed 16 Oct. 2024.

8. Subhan MA, Parveen F, Shah H, et al. “Recent Advances with Precision Medicine Treatment for Breast Cancer including Triple-Negative Sub-Type. Cancers (Basel).” doi: 10.3390/cancers15082204. PMID: 37190133.

9. Tung, N., Battelli, C., & Allen, B. "Clinical Applications of Next-Generation Sequencing in Breast Cancer."Oncology (Williston Park), 34(7), 274-285.