'Setting the Stage' in Breast Cancer

WHEN SOMEONE RECEIVES A cancer diagnosis, one of the first questions the patient or a family member asks the oncology team is: How advanced is the disease?

Staging is the process used to summarize how early or advanced a cancer is — whether or not it is curable and, if so, the approximate expected cure rate. Cancers in each area of the body have unique staging systems based on anatomy. In breast cancer, staging involves the size of the tumor and whether it has spread to nearby lymph nodes or other organs (known as metastasis).

Two types of staging are used: clinical and pathological. Clinical staging is done prior to surgery using physical examination and imaging such as mammogram, ultrasound, MRI and/or PET/CT scans. Pathologic stage is assigned after surgery has been performed and the tumor and lymph nodes have been evaluated.

In January 2018, the American Joint Committee on Cancer made significant changes to the breast cancer staging process. Previously, staging was determined strictly from tumor size (T), lymph node involvement (N) and metastasis to other organs (M). Each element was assigned a number from zero to 4, which were combined to give the stage, also described as a number from zero to 4.

As research has proved, tumor biology is an important factor in determining prognosis. To account for this, physicians now look to a patient’s pathology report and include the tumor’s grade and receptor status as factors in staging. The grade, which is determined when the tumor is viewed under a microscope, describes how similar or different the cells look compared with normal breast tissue, measured on a scale from 1 to 3. The receptor status is based on whether the tumor is driven by the hormones estrogen or progesterone or by the growth factor receptor HER2.

Being positive for estrogen and progesterone receptors is a favorable prognostic factor, because it makes patients eligible for five years of treatment with oral endocrine medications that can help decrease the risk of cancer’s recurrence.

HER2-positive tumors are aggressive, but research has brought effective therapy. For example, two targeted agents, Herceptin (trastuzumab) and Perjeta (pertuzumab), interfere with HER2’s activity. These powerful agents work in combination, along with chemotherapy, to shrink the tumor before surgery but are also used after surgery, and they have made the prognosis for patients with this disease subtype much better. Before Perjeta was approved, the introduction of Herceptin alone improved survival rates in this population by one-third. Now that grade and receptor status are considered along with tumor size and lymph node status, breast cancers can be more accurately staged, and this can be beneficial to patients. For instance, before 2018, tumors larger than 3 centimeters always had a stage of 2 or 3. But now, if the tumor has good prognostic features, such as being estrogen- or progesteronepositive, a tumor this size can be assigned a lower stage. For example, the stage has changed for a grade 2, 5.3-centimeter tumor that is nonmetastatic, has spread to one lymph node and is estrogen-, progesterone- and HER2-positive. Previously, this tumor would have been categorized as stage 3a. Now it’s considered stage 1b. A tumor with all the same characteristics except for its smaller size — 3 centimeters — previously would have been categorized as stage 2b but now is also considered stage 1b.

The improvements in treatments for breast cancer offer patients many advantages.

Evaluating the biologic makeup of a tumor can help oncologists better predict outcomes, assuming standard therapies are used. And seeing a lower stage number can give patients the inspiration and hope they need to stick with their treatments, improving their chances of survival.

Regina Hampton, M.D., FACS, is medical director of the breast center at Doctors Community Hospital in Lanham, Maryland, and a board member of the American Society of Breast Surgeons Foundation. The foundation hosts an informational website for patients, survivors and caregivers (breast360.org).