Identifying, monitoring, and treating women for breast precancer or cancer

Abstract

The invention is to methods for screening women for breast cancer and precancer by determining a level of an estrogen-related marker. The invention further provides methods of treating such patients identified as having one or more abnormal ductal epithelial cells and an estrogen-related marker. The invention provides methods for screening patient for hormone replacement therapy (HRT), and of monitoring such patients once they begin HRT. The invention provides methods of treating peri-, menopausal or postmenopausal women for both cancer risk reduction and menopausal symptoms (or other conditions related to lowered systemic estrogen levels). The invention also provides kits for the screening, monitoring, and treating methods described.

1 - 35 . (canceled)  
     
     
         36 . A method of monitoring a menopausal or postmenopausal woman on hormone replacement therapy (HRT) comprising: providing a ductal fluid sample from one or more ducts of a breast of a patient, and examining the ductal fluid sample for a precancerous or cancerous ductal epithelial cell, wherein indicated therapies for patients found to have one or more precancerous or cancerous epithelial cells include stopping HRT, reducing a dosage of hormone in the HRT, taking an estrogen activity modulator systemically, taking an estrogen activity modulator intraductally, switching to a different drug to reduce menopausal symptoms, and switching to a different drug to reduce bone loss.  
     
     
         37 . A method as in  claim 36 , wherein the precancerous ductal epithelial cell comprises a cell at a stage selected from the group consisting of ductal hyperplasia, atypical ductal hyperplasia, and low grade ductal carcinoma in situ (LG-DCIS).  
     
     
         38 . A method as in  claim 36 , wherein the cancerous ductal epithelial cell comprises a cell at a stage selected from the group consisting of high grade ductal carcinoma in situ (HG-DCIS) and invasive carcinoma.  
     
     
         39 . A method as in  claim 36 , further comprising examining the precancerous or cancerous ductal epithelial cells to detect the presence of an estrogen receptor, wherein the presence of an estrogen receptor indicates that the cell is hormone responsive.  
     
     
         40 . A method as in  claim 36 , wherein the action selected comprises taking an estrogen activity modulator, and the estrogen activity modulator is administered intraductally.  
     
     
         41 . A method as in  claim 40 , wherein the estrogen activity modulator comprises an aromatase inhibitor.  
     
     
         42 . A method as in  claim 36  or  39 ; further comprising assaying the ductal fluid for an elevated level of a marker selected from the group consisting of estrogen, an estrogen metabolite, aromatase enzyme, evidence of aromatase activity, biproducts of estrogen synthesis, and a protein effector acting upstream of estrogen synthesis; wherein indicated therapies for patients having an elevated level of one or more markers above normal include administration of a lower dosage of hormone in the HRT, close monitoring of markers while the patient is on HRT, close monitoring of ductal epithelial cell changes while the patient is on HRT, selecting an agent for HRT that provides a reduced cancer risk, stopping the HRT, and intraductal administration of an estrogen activity modulator to an affected duct or ducts.  
     
     
         43 . A method as in  claim 42 , wherein when a marker is elevated above normal, and the ductal epithelial cells are normal, the patient is directed to remain on HRT and be monitored periodically for changes in marker levels and ductal epithelial cell character.  
     
     
         44 . A method as in  claim 36 , wherein providing the ductal fluid sample comprises obtaining the sample from the breast.  
     
     
         45 . A method as in  claim 36 , wherein providing the ductal fluid sample comprises receiving a sample which has been previously obtained.  
     
     
         46 . A method as in  claim 36 , wherein the fluid was obtained by nipple aspiration or by ductal lavage of at least one milk duct.  
     
     
         47 . A method as in  claim 36 , wherein the fluid is collected from a single duct.  
     
     
         48 . A method as in  claim 36 , wherein examining the ductal fluid comprises cytological examination of ductal epithelial cells in the sample to determine whether they are precancerous or cancerous.  
     
     
         49 - 61 . (canceled)  
     
     
         62 . A method as in  claim 39 , further comprising assaying the ductal fluid for an elevated level of a marker selected from the group consisting of estrogen, an estrogen metabolite, aromatase enzyme, aromatase activity, a biproduct of estrogen synthesis, and a protein acting upstream of estrogen synthesis, wherein indicated therapies for patients having an elevated level of one or more markers above normal include administration of a lower dosage of hormone in the HRT, close monitoring of markers while the patient is on HRT, close monitoring of ductal epithelial cell changes while the patient is on HRT, selecting an agent for HRT that provides a reduced cancer risk, stopping the HRT, and intraductal administration of an estrogen activity modulator to an affected duct or ducts.