by Barbara Christie-Pope, PhD
Professor of Biology, Cornell College

Metastasis is the movement of cancer cells from a primary tumor to a distant site in the body. This simple definition does not capture the fear and devastation felt by an individual when they learn that they have metastatic disease. The initial reaction is, why did this happen? Why didn’t my therapy work? I thought I was “cancer-free”; how could this come back to haunt me ten years later? Is there something I did that caused this? The questions are endless and sometimes overwhelming.

Unfortunately, these questions lack answers. Around 90% of all cancer mortality is due to metastasis; therefore, research is necessary to treat metastatic disease and to prevent metastasis in the first place. The mechanisms underlying the development of metastatic tumors, often referred to as the metastatic cascade, is poorly understood but many avenues of research are piecing together the route tumor cells must travel to new sites in the body and, once there, how these cells respond to their new, foreign environment.

The cascade begins when a cell from the primary tumor detaches and enters the lymph circulation and on to the blood or enters the blood directly. This process requires the cells to navigate through the blood vessel wall, travel through the blood, then exit the blood vessel to gain entry to tissues. Tumor cells in the blood are met with a very hostile physical and cellular environment. These cells enter a fast-flowing river where they encounter obstacles such as the inner banks of the blood vessel wall. The shearing forces and pressure within the blood vessel can damage their fragile cell walls. Cells of the immune system are also found in blood. These natural killer cells are appropriately named and have the ability to recognize the tumor cells and destroy them. Unfortunately, platelets, small fragments of cells involved in blood clotting, can form a protective barrier around the tumor cells allowing survival and assisting with the exit of the tumor cells into the tissue surrounding the blood vessel.

Although thousands of cells may begin this arduous journey, few actually survive. This sounds like good news. But unfortunately, it only takes one seeding cell to begin the new formation of a secondary tumor.

In addition, these disseminated tumor cells, or DTCs, usually begin this cascade prior to detection of the primary tumor. Once leaving the blood and entering another tissue or organ, DTCs encounter a new environment, the so-called microenvironment, which contributes to and may determine their survival, their ability to stop multiplying and remain quiescent or dormant, and their resistance to therapy.

But, if cancer therapy is systemic or administered all over the body, how do DTCs escape this therapy only to revive and begin multiplying into a secondary tumor years to decades later? Because most cancer therapies target rapidly dividing cells, non-dividing DTCs are resistant to these therapies. We need strategies to target DTCs by either keeping them dormant and stopping their reactivation or destroying them. Current research is identifying the factors including proteins and genes that determine and regulate the interactions between DTCs and the environment surrounding them. Therapies that target these interactions could conceivably halt the recurrence of cancer. Unfortunately, there are no tests to determine where DTCs are in the body; therefore, it is challenging to determine whether or not an individual will experience metastatic disease.

DTCs are ticking time-bombs. Defusing these bombs is going to take more research and is a major therapeutic challenge. Want to find out more about how researchers are working to prevent or stop metastasis and death from cancer? On Tuesday, October 19, 2021, from 5:30-8:30 via zoom, Beyond Pink TEAM will feature Dr. Cyrus Ghajar, whose groundbreaking research into dormant cancer cells and the environments within which they may awaken is one of the most promising new developments in cancer research. Dr. Ghajar studies how the microenvironments within distant tissues regulate DTC dormancy and/or growth. He believes that solving these puzzles will allow the development of drugs that eradicate dormant DTCs before they can develop into full-blown metastases. He conducts this work within the Fred Hutchinson Cancer Center Laboratory for the Study of Metastatic Microenvironments.
​Register for the Ignite the Cancer Conversation event here.


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By Douglas M. Duven, M.D., F.A.C.S of the Breast Care Center

Fact: Men can carry and pass on the BRCA gene mutation.
Breast cancer occurs in men & women. Approximately one male is diagnosed for every 100 women. Male breast cancer often presents with a lump or mass. Mammograms are possible for men if indicated. Ultrasound assists in evaluating the male breast tissue. Biopsies are the same as for women – usually an ultrasound guided core biopsy. If a cancer is found, a mastectomy is usually recommended. Male breast cancer is also tested for estrogen and progesterone receptors, Tamoxifen is often prescribed for the ER+/PR + tumors. Men with a lump that is not centrally located (beneath the nipple) should be evaluated for a possible cancer

Fact: Men can carry and pass on the BRCA gene mutation.
The maternal side of the family used to be the focus, now both maternal and paternal sides need to be evaluated for breast, ovarian and pancreatic cancer. Many men develop a breast lump or enlargement that is not cancer.

Gynecomastia is the growth of male breast tissue, commonly located beneath the nipple. Male breast tissue can be affected by hormonal fluctuations and medical conditions. Gynecomastia can be a side effect of many medications, including testosterone supplements. Dietary supplements such as those used by body builders are also a possible source. Some medical conditions such as kidney disease/failure, prostate cancer also raise the incidence of gynecomastia.

Paget’s Disease of the breast is a malignancy, often presenting with a persistent rash, irritation or lesion of the areola or nipple. A punch biopsy of the lesion often is the most frequent biopsy type used to rule out Paget’s Disease. Paget’s can be non-invasive or invasive. Women should be encouraged to report any persistent rash or lesion of their breast to their primary care physician. Frequently, a steroid containing cream is prescribed initially. If there is no improvement using the cream, referral for biopsy is recommended. Paget's is treated with surgery. These tumors are tested for the estrogen and progesterone receptors, with anti-estrogen therapy often recommended. Chemotherapy may be indicated for an invasive Paget's tumor.

Malignant Phyllodes tumors account for less than 1% of breast cancers and typically present as a rapidly enlarging, palpable mass in middle-aged to older women, and may develop over several months. The mammographic appearance is often telling— a very large, relatively circumscribed, round or oval mass. The mass may become extremely large. At close inspection, the margins are often ill defined rather than sharply circumscribed. When detected at a screening examination, the appearance may mimic a fibroadenoma. The ultrasound appearance is similar to that of fibroadenoma, though a phyllodes tumor more frequently contains cystic spaces than does a benign fibroadenoma. On ultrasound, the margins of a phyllodes tumor are typically ill defined. Surgical treatment is similar to other breast cancers, lumpectomy when appropriate or mastectomy.

Inflammatory Breast Cancer is a rare, but aggressive form of breast cancer. Frequently, it presents with redness, swelling, tenderness and a warm sensation of the breast. Often this is initially mistaken for an infectious process. The swelling of the breast tissue and skin is due to the blockage of the lymph channels. The breast skin may have the appearance of orange peel. Often there is no specific mass palpated within the breast. Other symptoms are a rapid increase in breast size, heaviness and marked asymmetry. Ultrasound often shows significant skin edema.  Diagnosis is made by biopsy of the abnormal skin or by core biopsy of a lesion within the breast. Many inflammatory breast cancers are advanced before diagnosed, often with lymph node involvement, sometimes with distant metastasis. Inflammatory breast cancer is most frequently treated with aggressive chemotherapy prior to any definitive surgery. Hormonal therapy is used if the tumor is estrogen/progesterone receptor positive.

Mastitis is an infection of the breast. Frequently, women who are nursing have mastitis, but the condition is not limited to those women. Mastitis can occur at nearly any age. These infections can arise from a breast duct, the nipple can be the entrance site for common skin bacteria, the fluid in the ducts serves as a host for the bacteria. Redness, swelling, fever, and pain are the presenting symptoms. Sometimes, the infection can break through the skin or drain through the nipple. An ultrasound can help to detect an infected pocket of fluid, often this pocket can be drained. The fluid removed may be evaluated by the lab for the type of bacteria and which antibiotics will work best. Oral antibiotics are usually used and often need to be taken for an extended course to fully treat the infection. Surgical removal of the chronically infected area may be required if the mastitis recurs. Women who smoke have a higher incidence of mastitis.

Women and men should report any change(s) of their breast(s) to their physician.


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