Setting: office
CC: “My mammogram showed a lump.”
VS: normal
HPI: A 44-year-old woman who just had a mammogram that showed an abnormality comes to the office to find what the next step is. The patient’s mother and sister both had breast cancer so when she went to a random “health fair” in her neighborhood, she was advised to get a mammogram earlier than age 50. She feels well.
At what age is mammographic screening recommended for the general population?
a. At 35 years
b. At 40 years
c. At 50 years
Answer c. At 50 years
For women at average risk, screening mammography is recommended to begin by the age of 50 years. This patient should have been screened starting at least by age 40 years because of the very significant family history. A woman in the general population has a risk of 12% to 14% (1 in 9) without any family history. With two first-degree relatives, her risk is closer to 40% to 45%.
First-Degree Relatives
• Siblings
• Parents
PMHx/Medications: none
PE: normal
With her family history of breast cancer, besides starting screening early, which would be best to have prevented having breast cancer?
a. Breast cancer antigen (BRCA) testing
b. Tamoxifen
c. Breast ultrasound (US)
d. Breast magnetic resonance imaging (MRI)
e. Self-examination once a month
Answer b. Tamoxifen
Tamoxifen and raloxifene prevent breast cancer from ever occurring in the first place. These selective estrogen receptor modulators (SERMs) give a 50% reduction in the risk of breast cancer. They are used in those with two first-degree relatives who are at much higher risk of breast cancer than the general population. Breast US is used when a lump is detected in a younger, premenopausal patient and it is not clear if the lesion is solid or cystic. Breast MRI is useful in evaluating firm breasts with unusual architecture, but it is not clear that MRI is definitely better than mammogram. BRCA testing does not prevent cancer. BRCA is associated with the 10% of patients with familial breast cancer, but in this patient, we already know she is at high risk of cancer. In terms of the breast, it is not clear what BRCA offers.
SERMs stop cancer. BRCA tells risks without a clear therapeutic path.
Tamoxifen prevents breast cancer in high-risk patients.
BRCA testing benefit is not clear.
Initial Orders:
Needle aspiration biopsy
SERMs
• Antagonistic at breast
• Agonistic at:
Bone
Endometrium
Clotting factors
What is the absolute increase in risk of endometrial cancer after using a SERM for 5 years in 1000 women?
a. 1
b. 10
c. 100
d. 200
Answer a. 1
The absolute increase in the risk of endometrial cancer is about one new cancer over 5 years in 1000 treated women. Without SERMs, 1/1000 women get endometrial cancer in 5 years. With a SERM, it is 2/1000 women.
If you have a 40% risk of breast cancer in a high-risk person, that would be 400 breast cancers in 1000 women. With a SERM (e.g., tamoxifen) the number drops to 200. So, bottom line, you have one more endometrial cancer, and 200 less breast cancers.
SERMs decrease breast cancer risk much more than increase endometrial cancer risk.
Tamoxifen stimulates osteoblasts.
The patient returns after the breast biopsy, which shows infiltrating ductal adenocarcinoma of the breast.
Report:
Estrogen receptor (ER) positive
Progesterone receptor (PR) positive
No cancer on mammography of other breast
HER2/Neu antigen increased
Trastuzumab
• Monoclonal antibody
• Removes HER2/Neu positive cells
• Negligible adverse effects
• Prevents metastases
Which of the following should be done next?
a. Axillary lymph node dissection
b. Sentinel node biopsy
c. Bone marrow biopsy
d. Lumbar puncture
Answer b. Sentinel node biopsy
The “sentinel” node is the first node in the operative field (Figure 9-1). If this node shows no cancer, you do not need to do an axillary lymph node dissection. There is no need to do bone marrow biopsy or lumbar puncture in the routine preoperative or prechemotherapy evaluation of breast cancer. To find the sentinel node, contrast is put into the operative field. You then remove the first node that the contrast goes to and send it for immediate histologic examination.
Figure 9-1. Sentinel node. (Reproduced with permission from Giuliano AE.)
On computer-based case simulation (CCS), you cannot physically transfer the patient to a location called “Operating Room.” Order the procedure you feel is correct. The software will tell you if you also need a consultation to do the procedure. For example, if you order “Pap smear,” the CCS software lets you do the test. If you order “Colposcopy,” the software will tell you to get a gynecology consultation first.
As you have the results of the needle biopsy and mammography showing a unilateral, unifocal lesion, you should proceed to order the procedures you know are needed.
Orders:
Surgical consultation
Oncology consultation
Sentinel node biopsy
Lumpectomy
Radiation of breast tissue
Lumpectomy = Modified Radical Mastectomy Only if Breast is Radiated!
Without radiation to the breast, cancer recurs with lumpectomy alone.
The patient undergoes the procedure and the procedure report states: “Lumpectomy performed successfully, no cancer found in sentinel node; 2-cm infiltrating ductal carcinoma removed. Frozen sections show surrounding tissue free of cancer.”
The oncology and surgical consultation reports, as is usual on CCS, do not give specific recommendations or directions.
• If ER or PR is positive, give a SERM.
• SERMs and aromatase are more effective if both ER and PR are positive.
Which of the following will lower mortality the most?
a. Modified radical mastectomy (MRM) versus radical mastectomy
b. MRM versus lumpectomy and radiation
c. Adjuvant chemotherapy
d. Oophorectomy
Answer c. Adjuvant chemotherapy
Adjuvant chemotherapy provides a definite mortality benefit. MRM is not better than lumpectomy and radiation in most patients. Radical mastectomy is obsolete and never the right answer. Adjuvant means chemotherapy that is used to prevent metastases. It is not “prophylactic” because the person already has cancer. You will not be asked much at all about the different types of chemotherapy because it is not clear which therapy would be best for this patient.
Aromatase Inhibitors
• Anastrazole
• Letrozole
• Exemestane
Which of the following is the most common adverse effect of aromatase inhibitors?
a. Endometrial cancer
b. Osteoporosis
c. Bladder cancer
d. Ovarian cancer
Answer b. Osteoporosis
Osteoporosis occurs because aromatase inhibits estrogen production with side effects including bone loss. SERMs have an agonist effect on bone, and an antagonist effect on breast tissue, that is why tamoxifen and raloxifene are considered “selective.”
Aromatase Inhibitors
• Stop the conversion of testosterone to estrogen.
• Block the removal of one carbon from steroid nucleus testosterone.
• Work at the ovary and in adipose tissue.
• Simulate oophorectomy.
The patient undergoes radiation therapy to the breast after the lump is removed surgically. Because the lesion is >1 cm, chemotherapy is given. It is not clear whether to use a SERM or an aromatase inhibitor.
Treatments That Lower Mortality
• Surgery: MRM or lumpectomy with radiation
• HER2/Neu: trastuzumab if extra HER2 present
• Adjuvant chemotherapy
• SERMs or aromatase inhibitors
Aromatase inhibitors inhibit osteoblasts.
To provide blockage of estrogen in premenopausal women, leuprolide and goserelin are sometimes given to prevent the need for oophorectomy. How do they work?
a. They block luteinizing hormone (LH) and follicle-stimulating hormone (FSH) on the ovary.
b. They decrease the release of LH and FSH from the pituitary.
c. They decrease the level of adrenal androgens.
d. They block the peripheral conversion to estrogen.
Answer b. They decrease the release of LH and FSH from the pituitary.
These medications are gonadotropin-releasing hormone (GnRH) agonists. They will block FSH and LH release.