Infiltrating Duct Carcinoma of Breast – additional opinion
Short Summary

51-year-old female was diagnosed with stage I, Grade I infiltrating duct carcinoma of the breast. Estrogen receptors were highly positive and Progesterone receptors negative. Based on these findings the expert advises that she receive adjuvant radiotherapy and hormonotherapy. The adjuvant hormonotherapy consist of initial treatment by Tamoxifen for 2 years, thereafter switched to an Aromatase Inhibitor. The expert also informs the patient about potential side effects of Tamoxifen treatment, which are not frequent and generally mild.

Patient's Questions
The patient would like to get additional information as to possible side effects and complications related to the Tamoxifen treatment.
Medical Background

The patient underwent surgery for her breast cancer on 2/2009. This was a stage I, Grade I infiltrating duct ca. The Immune-histochemical parameters were Her-2/neu negative; Estrogen receptors highly positive and Progesteron receptors negative.

Expert's Opinion

Based on these findings I advised that she receive adjuvant radiotherapy and hormonotherapy. The last is used to be started by Tamoxifen for 2 years, then switched to some Aromatase Inhibitor at the discretion of the treating oncologist (whether Anastrozole, Letrosole or Exemestane) up to a total of five years hormonotherapy.
Although the same advice was offered by her oncologist I understand that the patient would like to get additional information as to possible side effects (complications?) related to the Tamoxifen treatment.
 
DISCUSION:
1)    The advice of the treating oncologist was properly individualized according to the patient's tumor characteristics. The main character of her tumor is represented by the richness of Estrogen Receptors which classify the tumor as hormonosensitive. This means that estrogen deprivation should be induced in order to minimize the risk of tumor recurrence. In fact, the results of the Oncotype testing corroborate this "statement". They showed, based on the tumor genes, that the recurrence score is 16 which is in the low range, with about only 10% risk of distant metastases following 10 years of follow up. However, this low figure belongs to similar tumors provided that they had been treated by adjuvant Tamoxifen for five years. Without such treatment the results might be worse.
It should be clarified that the figures obtained by the oncotype analysis took into consideration the negativity of progesterone receptors. Although this negativity diminish to some degree the benefit of hormonotherapy, it still leaves a major role for its application based on the clear estrogen positivity.
2)    The current guidelines for adjuvant hormonotherapy, as followed both in the USA and in Europe for best estrogen deprivation in postmenopausal women, consist on initial treatment by Tamoxifen for 2 years, as blocker of estrogen receptors on potentially remaining tumor cells, thereafter switched to an Aromatase Inhibitor, which suppresses estrogen production by the adrenal glands.

3)    With regards to potential side effects of Tamoxifen treatment, these are NOT frequent and are generally mild. Nevertheless, the patient has to be informed about them:
a)    HOT FLASHES. If these occur significantly as to impair the quality of life, they may be treated by non hormonal measures such as Tab. Clonirit or Tab. Efexor. Only very few patients are intolerant to Tamoxifen due to this side effect, and these can be offered an earlier switch to the aromatase inhibitor although the hot flashes may still persist to some degree.

b)    ENDOMETRIAL CARCINOMA: The incidence of this second tumor has been reported to increase following Tamoxifen treatment. However, this was directly related to the length of treatment: mainly five and not only two years of treatment. Furthermore, much endometrial curettages have been performed for analyzing the nature of endometrial thickening which invariably occurs along Tamoxifen treatment. It was concluded that this is a benign phenomenon which reverses on stopping Tamoxifen treatment. Therefore only regular follow up is required, with curettage reserved to cases of vaginal bleeding. With awareness to the possibility of endometrial cancer, even a minimal vaginal bleeding should induce stopping Tamoxifen treatment accompanied by gynecological investigation. By such measures, even the very few endometrial cancers appearing in this population are usually diagnosed and treated at an early and curable stage.

c)    Hypercoagulability and possible DEEP VEIN THROMBOSIS (DVT):
It is advised that Tamoxifen treatment should not be offered to patients with past history of hypercoagulability events, especially that of deep vein thrombosis. Similarly, it is advised that treatment be stopped for a few days towards long distance flights in order to prevent this complication. At any rate, if under treatment there appear pain and/or swelling, especially bellow knee, treatment should be stopped an a Doppler test should be performed as soon as possible in order to diagnose DVT and to offer effective treatment.
d)    It is stressed that these "alarming" side effects are taken into consideration
when Tamoxifen is prescribed, and PRACTICALLY this is considered a       relative safe treatment, especially when the patient is aware of physical       changes and seeks assistance if and when they occur. Furthermore, the       limitation of treatment to two years is meant to decrease these side effects.
 
NOTE: The results of the CYP2D6 analysis showing that the patient is an extensive metaboliser ensure that she does not belong to the 10% of patients ineffectively treated by Tamoxifen, rather that this treatment be effective for her.
In conclusion, the potential benefit from Tamoxifen treatment is usually greater than the potential risks. At any rate, decisions regarding treatment should be individualized on the basis of each patient's characteristics and preferences, following a thorough discussion with the treating oncologist.

""