Focusing light on breast cancer diagnostics

A team of scientists at the Massachusetts Institute of Technology (MIT), comprising principally of Dr. Ishan Barman, Dr. Narahara Chari Dingari and Dr. Jaqueline Soares, and their clinical collaborators at University Hospitals, Cleveland have developed the Raman scattering-based concomitant diagnosis of breast cancer lesions and related micro-calcifications.

Let’s find out more about this new breast cancer research done by the team at MIT.

Early detection necessary!
According to MIT, one in eight women in the US will suffer from breast cancer in her lifetime and breast cancer is the second leading cause of cancer death in women. Worldwide, breast cancer accounts for 22.9 percent of all cancers (excluding non-melanoma skin cancers) in women. In 2008, breast cancer caused 458,503 deaths worldwide (13.7 percent of cancer deaths in women).

Therefore, technological advancements for its early detection and subsequent treatment can make a significant impact by preventing patient morbidity and mortality and reducing healthcare costs, and are thus of utmost importance to society. Currently, mammography followed by stereotactic breast biopsy serves as the most promising route for screening and early detection of cancer lesions.

Nearly 1.6 million breast biopsies are performed and roughly 250,000 new breast cancers are diagnosed in the US each year. One of the most frequent reasons for breast biopsy is microcalcifications seen on screening mammography, the initial step in early detection of breast cancer. Microcalcifications are micron-scale deposits of calcium minerals in breast tissue that are considered one of the early mammographic signs of breast cancer and are, therefore, a target for stereotactic breast needle biopsy.

However, despite stereotactic guidance, needle biopsy fails to retrieve microcalcifications in one of five breast biopsy patients. In such cases, the resulting breast biopsies are either non-diagnostic or false-negative, thereby, placing the patient at risk and potentially necessitating a repeat biopsy, often as a surgical procedure.

There is an unmet clinical need for a tool to detect microcalcifications in real time and provide feedback to the radiologist during the stereotactic needle biopsy procedure as to whether the microcalcifications seen on mammography will be retrieved or the needle should be re-positioned, without the need to wait for a confirmatory specimen radiograph.

Such a tool could enable more efficient retrieval of microcalcifications, which would, in turn, minimize the number of x-rays and tissue cores required to achieve a diagnostic biopsy, shorten procedure time, reduce patient anxiety, distress and discomfort, prevent complications such as bleeding into the biopsy site seen after multiple biopsy passes and ultimately reduce the morbidity and mortality associated with non-diagnostic and false-negative biopsies and the need for follow up surgical biopsy.

If 200,000 repeat biopsies were avoided, at a cost of $5,000 per biopsy (a conservative estimate and would be much higher for surgical biopsies), a billion dollars per year can be saved by the US healthcare system. The MIT Laser Biomedical Research Center, has recently performed pioneering studies to address this need by proposing, developing and validating Raman and diffuse reflectance spectroscopy as powerful guidance tools, due to their ability to provide exquisite molecular information with minimal perturbation.

Specifics of the technique
Stating the specifics of the technique developed by MIT, the team said that their research focuses on the development of Raman spectroscopy as a clinical tool for the real time diagnosis of breast cancer at the patient bedside. “We report for the first time development of a novel Raman spectroscopy algorithm to simultaneously determine microcalcification status and diagnose the underlying breast lesion, in real time, during stereotactic breast core needle biopsy procedures.”

In this study, Raman spectra were obtained ex vivo from fresh stereotactic breast needle biopsies using a

compact clinical Raman system, modeled and analyzed using support vector machines to develop a single-step, Raman spectroscopy based diagnostic algorithm to distinguish normal breast tissue, fibrocystic change, fibroadenoma and breast cancer, with and without microcalcifications.

The developed decision algorithm exhibits a positive and negative predictive value of 100 percent and 96 percent, respectively, for the diagnosis of breast cancer with or without microcalcifications in the clinical dataset of nearly 50 patients.

Significantly, the majority of breast cancers diagnosed using this Raman algorithm are ductal carcinoma in situ (DCIS), the most common lesion associated with microcalcifications, which has classically presented considerable diagnostic challenges.

This study demonstrates the potential of Raman spectroscopy to provide real-time feedback to radiologists during stereotactic breast needle biopsy procedures, reducing non-diagnostic and false negative biopsies. Indeed, the proposed approach lends itself to facile assembly of a side-viewing probe that could be inserted into the central channel of the biopsy needle for intermittent acquisition of the spectra, which would, in turn, reveal whether or not the tissue to be biopsied contains the targeted microcalcifications.



Is this a powerful biopsy tool?
Well, is this merely a powerful biopsy guidance tool for the near future or more than that?

According to the MIT team, in the immediate future, they see the proposed spectroscopic modalities as extremely powerful biopsy guidance mechanisms. Additionally, suitable application of spectroscopy can provide rapid and reliable intraoperative margin assessment of excised surgical specimens.

In breast conserving surgery, for example, re-operation for positive margins discovered after surgery (i.e., presence of tumor cells) is required in up to 50 percent of cases, which can be avoided on suitable application of spectroscopy.

Finally, in the long run, the team envisions that spectroscopy can provide the necessary molecular imaging information which can allow it to compliment, or even substitute, histopathological examination.

Assuming this is a study, how long it will take to go commercial?

The team at MIT strongly believes that given the extensive testing of its methods in over a hundred patients and the impressive nature of results, translation of this technology to the clinical domain should not take substantive time. Further, since they did not introduce any exogenous contrast agents or dyes, clearance from FDA is also likely to be simpler. This has the potential to be incorporated in the suite of biopsy tools in the next two to three years.

Likely costs!
What are the likely costs required in treatment of a patient?

At this time, there are complex layers related to the fundamental question: “who pays for the additional modality in the biopsy procedure”? Insurance and re-imbursement issues would form a critical part of the overall answer. However, given the probability of avoiding a second, repeat biopsy, it would be far more cost-effective in the long run.

Will women recover?
Finally, what are the chances of women recovering, post treatment?

Accurate, early detection of cancer lesions can significantly bump the recovery and survival rates of women

 with breast cancer. There are no additional risk factors from the incorporation of spectroscopy in the biopsy procedure as there is only low-power laser irradiance.

How credible is the Raman spectroscopy technique in tackling breast cancer?

Optical imaging and, specifically, molecular imaging represent the new frontiers in diagnosis of cancer lesions. Raman spectroscopy is one of the most promising alternatives in this regard due to its ability to provide real-time, multiplexed bioanalyte information without necessitating addition of exogenous contrast agents.

On a personal level, I am very grateful to the team of MIT scientists for choosing me to report on such an extraordinary piece of scientific work! I am also hoping that a lot of women, especially those among my friends, do find some time and read this article and hopefully, benefit!