Diagnosis of HER2+/ER- Early Breast Cancer

Hope S. Rugo, MD:So, this patient is a 53-year-old woman who finds a large mass in her left breast on self-examination while she’s in the shower. And she had had a mammogram about 8 months previously, which was unremarkable, but showed very dense breasts. She comes in to see a breast surgeon after being referred from calling her primary care physician. The breast surgeon finds that her past medical history is unremarkable. She doesn’t have any family history of breast cancer, certainly not in her first-degree relatives. And then on physical examination, she has a 6 x 5-cm mass in the upper outer quadrant of the left breast without nipple changes, but with a little bit of retraction of the skin, and in her left axilla, you can feel several mobile axillary nodes that are firm and highly suspicious. Her review system is otherwise clear, and the rest of her examination is unremarkable.

She then goes and gets a mammogram and ultrasound. This new mammogram shows a spiculated mass that’s poorly defined. Ultrasound shows a 5.3-cm solid mass and enlarged axillary lymph nodes, 2 of them in the left axilla that have a thickened cortex, so they were highly suspicious. So, she has a core needle biopsy done of the breast mass and a fine needle aspiration of the left axilla. The core needle biopsy shows a high-grade invasive ductal cancer that’s hormone receptor-negative andHER2/3+ by IHC. The tumor is sent on to have FISH testing—although certainly not required with an IHC ofHER3+—and the FISH is also positive, with a copy number forHER2of 15 and a ratio to centimeters of 17 of 7.

The FNA of her axillary lymph node shows carcinoma consistent with node-positive disease. So, the stage turned out to be a T2 and 1M0 tumor essentially. And she undergoes staging studies that don’t show any evidence, and neither does her history, of any metastatic disease.

My impression of a patient like that when they come in—and I usually see them alongside the surgeon since I’m not seeing them first as a surgeon—is that this is a kind of cancer that we predict to be very sensitive to systemic therapy. We know the tumor needs systemic therapy. And if I know that a cancer needs chemotherapy, I would always prefer to give it before surgery, rather than after surgery, to improve surgical options and the cosmetics of surgery, but most importantly, for me as an oncologist, to have a better sense of how the tumor is responding to therapy for clinical trial considerations and for considerations of treatment that we have available in our armamentarium.

So, I would discuss with that patient the results, the biology of the cancer, and its high responsiveness to treatment, which makes it, in some ways, a better prognosis cancer than some of the cancers we used to think about as being better prognosis, but that continue to relapse for 20 years, like the hormone receptor-positive cancers. This one is all up front, and giving the chemotherapy and antibodies directed againstHER2would be my preference of an initial thinking to give to her to say, “Neoadjuvant therapy here is really the best way to go forward.”

Transcript edited for clarity.

• A 53-year-old woman was referred to a breast surgeon after finding a mass in her left breast
  • PMH: unremarkable
  • FH: no history of cancer in first-degree relatives
  • PE: revealed a 6 X 5-cm, non-fixed mass in the left inferior breast without skin changes or nipple discharge, and palpable lymphadenopathy in the left axilla
  • ROS: clear
• Mammogram confirmed a left-sided, poorly defined spiculated mass. Ultrasound shows a 5.3-cm solid mass and enlargement of 2 left axillary nodes with thickened cortex
• Pathology results:
  • Core needle biopsy from the breast mass confirmed grade 3 invasive ductal carcinoma
    • ER—,PR—,HER2IHC 3+
    • FISH,HER2copy number, 15;HER2:CEP17 ratio, 7
  • Fine-needle aspiration of one left axillary lymph nodes was positive for carcinoma
• Staging: T2bN1M0