Decreasing Breast Cancer False Positives with NV-VPAC1-PET Scan Technology

A doctor examines mammogram snapshot of breast of patient on the monitors.
A doctor examines mammogram snapshot of breast of patient on the monitors.

Despite technological advancements in the healthcare industry, breast cancer remains a major health problem. Self-examination and annual screening mammograms continue to be the most common methods used for early detection. Although cancer screenings have become a controversial topic, the importance of early diagnosis is undisputed [1][2]. Nevertheless, there is a critical need to further develop diagnostic breast imaging techniques that can distinguish which masses pose a threat, and which do not.

False Positives: Why Do They Occur?
The continued high rate of false-positive breast cancer screenings is largely the result of outdated technology. For example, screening mammograms most often detect benign cysts, calcifications and infections which may lead to false-positive breast cancer diagnoses. Positron Emission Tomography (PET) provides receptor specific tumor imaging–this allows distinction between benign (cancer-free) and malignant (cancer-positive) tumors and provides a more accurate demonstration of the state of malignancy.

In 2019, it is estimated that there will be 331,530 new cases of breast cancer and 41,760 breast cancer deaths among women in the U.S. [16]. In the U.S. male population, although rare, there will be approximately 2,670 new breast cancer cases and 500 breast cancer deaths in 2019 [16].

Sixty-one percent of women who begin annual mammography screening at 40 to 50 years of age have a 10-year cumulative risk of having at least one false-positive mammogram [3]. The cumulative risk for women who start annual screening later in life (66 to 74 years) is approximately 50 percent [4].

Invasive Procedures
Neither self-examination nor mammography can always distinguish between masses that are malignant and those that are benign. This inability compels physicians to perform invasive procedures–such as biopsies–on patients to obtain tissue samples for histology. This process remains the gold standard for determination of malignancy. Among the estimated 7 million breast biopsy procedures performed annually on women in the U.S., nearly 80 percent find benign pathology [5].

It has been estimated that among U.S. women aged 50 years who have been screened annually for a decade, 3 to 14 out of 1000 will be over diagnosed and treated needlessly. On the other hand, only 0.3 to 3.2 will avoid a breast cancer death [6]. Invasive biopsy procedures are associated with enormous health care costs, emotional trauma to patients, risks of spreading cancer and cosmetic concerns.

Biopsies and tissue histology unequivocally determine malignancy. Unfortunately, this procedure is largely based upon morphologic modulations that the cancerous cells undergo. There are characteristic fingerprints that occur prematurely in the malignant cells that can also point to signs of cancer, including:

• Excess hormone production
• Receptors or proteins found on the cell surface
• Oncogenes produced within the nucleus of the cell

These signs are silent, frank evidence of tumor growth that often go undetected because of their immaturity in comparison to the histology testing.

Confirmatory Testing
VPAC1 receptors are named for the combined vasoactive intestinal peptide (VIP) plus the pituitary adenylate cyclase-activating peptide (PACAP) family of cell surface receptors.
The VPAC1 receptor is classified as a Type II binding site of the PACAP receptor family [8][9]. The human VPAC1 receptor gene encodes a G protein-coupled receptor that recognizes both VIP- and PACAP-related peptides with high affinity [8][9]. VPAC1 receptors are overexpressed in numerous cancers, including prostate, breast, colon, liver, lung, pancreatic, bladder, thyroid and uterine cancer [10].

The overexpression of VPAC1 receptors occurs on the surface of malignant cells and precedes histologic changes [11, 12]. Breast cancer cells are said to express approximately 104 receptors per cell [11][13] [14]. VIP and PACAP have been shown to activate adenylate cyclase, increase VEGF (vascular endothelial growth factor) expression and secretion, and stimulate growth in various breast cancer cell lines [10].

NV-VPAC1 targets VPAC1 receptors, which are overexpressed on the surface of cancer cells early in the onset of cancer. Because these receptors play a major role in the progression of a number of malignancies, they may serve as molecular targets for cancer diagnosis and treatment.

VPAC1-specific peptides were designed and synthesized by Dr. Mathew Thakur and colleagues. Their hypothesis suggests that radiolabeled biomolecules with a high affinity for VPAC1 receptors could be used in vivo to image breast cancer cells. This breakthrough technology aids in both the early detection and localization of cancer cells. On the basis of its high affinity for VPAC1 receptors, 64Cu (Copper-64, a Beta-emitting isotope with a half-life [t½]=12.8 hours), was more sensitive than other imaging modalities, identifying all malignant tumors that overexpressed VPAC1, and did not identify benign tumors that did not overexpress VPAC receptors.

The Numbers
Approximately 40 million mammograms are conducted annually in the U.S. It is estimated that 1.7 million of those mammograms result in biopsies of suspicious lesions. Of those 1.7 million biopsies, approximately 1.3 million, or 80 percent, result in a benign diagnosis.

The estimated cost of those negative biopsies is nearly $4 billion.

NV-VPAC1® PET scan technology can significantly reduce the number of negative biopsies, improve the immediacy of a breast cancer confirmation and decrease the false positive rate.


References
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[16] American Cancer Society. Cancer Facts and Figures 2019. Atlanta, GA: American Cancer Society, 2019.