Patrick Neven, MD, PhD
|Patrick Neven, MD, PhD|
In Flanders, Belgium, only 2% of all breast cancers are diagnosed in patients younger than 36; therefore, it is a rare disease with fewer than 100 cases diagnosed each year in a region of 6 million inhabitants. For these younger patients, both "the disease" and "the diseased" differ respectively from "breast cancers" and "women with breast cancer" at an elder age. Both age and tumor type are prognostic.
At the Katholieke Universiteit Leuven (UZ Leuven), we have fairly specific criteria we follow for patients in this age group who have a palpable breast lump regarding diagnosis and local treatment. Imaging always starts with a breast ultrasound. UZ Leuven policy is to avoid using mammography unless there is a proven malignancy (two views). Without a proven malignancy, the clinician might request a mammogram following ultrasound if he or she suspects a solid lesion or is aware of a suspicious cyst. In this case, only one oblique view per breast is advised.
Ultrasound differentiates between a cystic lesion, which does not require follow-up, and a solid lesion, which does require follow-up. In a patient age 30 or younger, a solid lesion with the typical ultrasound appearance of a fi- broadenoma (often multiple) only requires follow-up after 6 months; the solid lesions often disappear spontaneously and are only removed if they grow or cause symptoms. In cases of familial/genetic breast cancer risk, we also require histology for those patients younger than 30, which we obtain by fine needle aspiration cytology or by core biopsy. Any (new) solid breast lesion in a patient age 30 or older requires a triple diagnostic evaluation: clinic examination, imaging, and pathology.
Excision is required in the following indications: growing fibroadenoma, hamartoma, (excluding phyllodes tumor), any papilloma and in case there is discordance between the clinic, imaging and pathology. A breast cyst is never excised (less than 20% of breast cysts recur following evacuation) unless ultrasound shows a suspicious intracystic lesion (thickened wall, polypoid intracystic appearance) when excision is performed.
We also advice a "wait and see policy" in case of non-growing fibroadenoma, hamartoma, lactating adenoma, and mastitis (cave granulomatous mastitis that requires corticosteroids).
The ER-Positive "Tumor Paradox"
When looking at the data stored in the UZ Leuven database on the 135 cases of breast cancer in women younger than 36 diagnosed between 2000 and 2009, only the mean tumor diameter didn't differ with age. We didn't have low-grade or lobular breast cancers in this young group. Breast cancers were more likely triple negative (ER, PR, and HER-2 negative), luminal B1- like (ER positive, HER-2 negative, and grade 3) and HER-2 positive with a 2.5, 2.2, and 1.7 frequency, respectively, when compared with tumors diagnosed in patients older than 35.
In this young age group, the ER-positive "tumor paradox" was also seen in this series. Women with an ER-positive tumor were more likely to relapse within the first 10 years than those with a triplenegative disease. Age is not a contraindication for breast conservative surgery, but the likelihood of local relapse is age dependent; between 1% and 2% per year of follow-up for patients younger than 40 at diagnosis. The EORTC 22881/10882 Boost Trial noticed a higher local relapse rate in the group without a radiation boost, and the beneficial effect of the boost is larger for patients younger than 40. For patients 40 and younger who receive a boost, there remains a 13.5% chance of developing a local relapse at less than 10 years of follow-up.
If a mastectomy has been performed, tumor type (triple negative) and disease extension are more prognostic for a local relapse than young age. This should be reflected when indicating postmastectomy radiotherapy, which should be independent of young age. Young age is also not of importance when selecting patients for the sentinel lymph node procedure.
Young age is an important predictive factor when considering the absolute benefit from adjuvant chemotherapy. Despite this observation, clinical trials must be performed to improve prognosis. Breast cancers are more likely of a specific type (e.g., medullary) and age-specific markers must be explored in order to tackle more specific targets (RANKL has been suggested). The effect of adjuvant tamoxifen starting 3 weeks after chemotherapy for patients with ER-positive disease is age independent. Patients should be counseled regarding appropriate contraception because amenorrhea (even if greater than 12 m) doesn't equal menopause. Also, aromatase inhibitors (AIs) are contraindicated unless ovarian function is suppressed but even then, tamoxifen is superior to these agents.
In case there is a demand for pregnancy, we advise at least a 2-year disease free interval; tamoxifen is best given during 5 years but must be stopped when pregnancy is allowed. Ongoing trials are examining to what extent ovarian suppression is indicated if women receive tamoxifen. With our current chemotherapy schedules, there is little chance to see chemotherapy-induced amenorrhea in patients younger than 36. There is no proven benefit on pregnancy rates when GNRH analogues are given together with the chemotherapy, but chemotherapyinduced ovarian failure is possible between ages 30 and 35. We always counsel these patients in our fertility clinic; all possible means to ensure future fertility are discussed, such as preservation of ovarian tissue, a prechemotherapy IVF cycle, and oocyte cryopreservation.
About the Author: Dr. Neven is a professor and practicing oncologist at Katholieke Universiteit Leuven, Belgium. He specializes in breast cancer care, and he is a member of the Multidisciplinary Breast Centre in Leuven University Hospitals. In 2009 he was elected President of the FGOG. Dr. Neven will be presenting information on managing menopausal symptoms in patients with breast cancer during today's General Session VII on survivorship.
This Expert Editorial was first published in 2012 Breast Cancer Symposium Daily News