In recent years, breast cancer has become a major problem in the global community and is the second leading
cause of cancer deaths among women (Sun et al., 2017). Breast cancer is a type of metastatic cancer (cancer
that spreads throughout the body) that originates from breast tissue, specifically the inner lining of milk
ducts or lobules that provide the ducts with milk (Sharma et al., 2010).
In Japan, despite advances in medical technology and emphasis on a healthy lifestyle, the incidence of
breast cancer has risen yearly (Ohno et al., 2013). In fact, the projected breast cancer incidence in Japan
was estimated at 92,300 in 2020, accounting for approximately 20% of all cancer cases in women (Katanoda et
al., 2014). Current breast cancer testing methods, such as mammograms and breast MRIs, can be uncomfortable
and expensive, which creates a stigma around testing that discourages early screening rates. In Japan, the
screening rate for women over the age of 40 is only about 40% (Sceaphierde, 2021). These statistics raise
the urgent need for early and widespread diagnosis of breast cancer in Japan.
With the most common form of breast cancer among Japanese women being triple-negative, there is a strong
demand for novel detection methods that can function even in the absence of common biomarkers such as
estrogen receptors, progesterone receptors, and HER2 protein (Takabe 2017). Triple-negative breast cancer is
an aggressive subtype of breast cancer where the cells test negative for the most commonly established
biomarkers. This causes hormonal therapy and HER2-targeted medicines to be ineffective and results in tumor
metastasis — one of the greatest challenges of cancer biology. The lack of targeted therapies and poor
prognosis for triple-negative breast cancer raises the importance of effective detection and early treatment
approaches (Kumar & Aggarwal 2015).
Literature has shown that early detection of breast cancer has caused the 5-year relative survival rate of
breast cancer patients to be above 80% (DeSantis et al., 2016). Therefore, ASIJ iGEM will focus on
developing an efficient method for breast cancer diagnosis.
Breast cancer is a type of cancer that occurs when cells in the breasts proliferate and spread abnormally, often forming a tumor that feels like a lump and can be detected with an x-ray. Although breast cancer primarily affects women, it can occasionally affect men as well. Most breast cancers begin in the ducts that carry milk to the nipples and are classified as ductal cancers, while breast cancers that start in the glands that make breast milk are classified as lobular cancers. Invasive ductal carcinoma (IDC) is a cancer that begins in the milk duct and invades breast tissue outside of the duct. It is the most common type of breast cancer, with 80% of all breast cancer patients being diagnosed with IDC (Ullah 2019). Breast cancer can metastasize—or spread to other parts of the body—when affected cells break away from the primary tumor and travel through blood and lymph vessels. It may spread to any part of the body, but most often spreads to the bones, liver, lungs, and brain (Libson & Lippman 2014). Common signs of breast cancer are breast lumps, changes in appearance (e.g., size and shape) of the breast or nipple, and redness or pitting of the skin over the breast (Mayo Clinic).
Existing methods of breast cancer detection and diagnosis include ultrasound, mammogram, MRI, and biopsy.
Breast ultrasound is a noninvasive technique that uses a transducer that is pressed against the skin to send
and measure sound waves that bounce off internal organs. This allows the radiologist to visualize the
internal structure, size, shape, and consistency of the breast to detect any abnormalities or lumps that may
be indicators of breast cancer (radiologyinfo.org). In contrast, mammograms rely on a machine that takes a
series of X-ray images to look at breast tissue. The machine compresses the breast using two plates, which
allows the X-rays to easily go through the tissue and lowers radiation exposure. Mammograms can detect
breast cancer by showing physicians abnormal changes in breast tissue (Mammogram Basics, n.d.). MRIs
(Magnetic Resonance Imaging) use a combination of radio and magnetic waves to show detailed pictures of the
breast and do not use radiation. Typically, MRIs can capture smaller breast lesions that mammograms miss
(Hopkins Medicine). Unlike MRIs, biopsies are more invasive and require procuring a sample of breast tissue.
Surgical and core needle biopsies are more invasive and are used to remove small cylinders of tissue or
parts of lumps in the breast. Fine needle aspiration biopsies are used to remove a small sample of tissue to
determine if it is cancerous. Some biopsies require the use of an ultrasound device to locate a mass and
then take a sample of tissue for analysis (Mayo Clinic). Among these methods, only the first three are
normally used during periodical checkups. In Japan, insurance only covers breast examinations conducted by
mammogram or ultrasound. MRIs are not covered by insurance and often cost over five times as much
(Nihonbashi Kenshin Center).
Although it is recommended that women—middle-aged and above—should be screened approximately once every one
or two years (on top of regular self-checks), only 44.9% of Japanese women aged 40 to 69 registered for an
examination within the two years leading up to 2016 (知っておきたいがん検診, n.d.). Given that breast cancer has been a
growing issue within Japan since the 1900s, this statistic poses to be a significant concern today
(Yonemoto, 1980).
Based on the raised issues regarding the current methods of detection, our goal is to create a convenient
breast cancer testing kit that is minimally invasive. This testing kit would make testing more accessible,
less invasive, and more affordable for women of all ages. Through our testing kit, we hope to make early
screening and detection rates significantly higher, and allow women to go through a pain-free and simple
process that is reliable and accurate to detect breast cancer.
We decided to employ aptamers, which are single-stranded oligonucleotides, to help detect our biomarkers.
Aptamers are significantly cheaper and easier than utilizing conventional antibodies and will help in our
development of a convenient test kit (Lakhin et al. 2013).
In addition, we have designed a fluorescent aptamer probe that can change conformation and fluorescence upon
binding with our biomarkers of interest, Mucin 1 and CA 15.3. By comparing this readout with a standard
curve, it thus becomes possible to ascertain the amount of biomarker in the sample without any washing or
separation through liquid biopsies. Although the readout was conducted on a 96-well plate reader in the lab,
we believe that a simple device involving an excitation laser and an emission recorder can be suitably
developed in the future for liquid biopsies. Experiments have shown that this technology can deliver results
with satisfactory sensitivity and specificity. We envision that this test will be applicable to a wide range
of bodily fluids potentially containing breast cancer biomarkers, including urine, saliva, sweat, tears, and
serum. As all these fluids can be harvested with minimal discomfort, this design offers a promising
alternative to traditional breast cancer detection methods.
We believe that our current detection system holds great potential, as it offers the sensitivity and
specificity of traditional immunoassays (such as ELISA) without requiring long incubation periods or washing
buffers. Furthermore, this kit is easy to store and relatively stable. This allows for the kit to be
realistically administered in a clinical setting on a large scale, even in far-flung or underserved areas.
Although the biomarkers we have identified are not currently recognized as suitable for diagnosing breast
cancer through liquid biopsies alone, we nonetheless still believe that in the future, advances in biomarker
research will allow for this technology to be extensively used in the early diagnosis of breast cancer.
