Title of Invention: GENETIC ALTERATION ASSOCIATED WITH PRE-MALIGNANT CANCER Abstract: Described herein are progenitor cancer cells and cell lines isolated from human breast ductal carcinoma in situ (DCIS) lesions and the uses of these cells or cell lines in drug design, drug screening, and monitoring in vivo therapy. The DCIS malignant precursor cells or cell lines are epithelial in origin, are positive for markers of autophagy, show at least one genetic difference from normal cells of said fragment, form 3-D tube-like structures or ball aggregates, or are inhibited in formation of 3-D structures and migration by treatment with chloroquine. In one embodiment, there is a loss of heterozygosity (LOH) that is narrowly confined to a region of chromosome 6p (6p21.1-6p12.3) that contains the SUPT3H gene. Detailed Description: CROSS-REFERENCE TO RELATED PATENT APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 61/256,063, filed Oct. 29, 2009, which application is incorporated by reference in its entirety. INTRODUCTION Ductal Carcinoma In Situ (DCIS) is the most common type of malignant precursor of breast neoplasia in women [1-4]. DCIS accounts for an estimated 30% of the 185,000 breast cancers detected by mammography each year. While the majority, if not all, invasive breast carcinoma emerges from a premalignant stage, only one in five DCIS lesions recurs as metastatic carcinoma [5, 6]. New therapies are needed for the improved treatment of premalignant breast lesions such as DCIS. If the new therapy is relatively non-toxic, then the therapy could be applied within a neoadjuvant regimen or a chemoprevention regimen. Despite this clinical need, two serious challenges exist: a) very little is known about the molecular origin of DCIS and the transition from in situ to invasive breast cancer, and b) it is impossible to rapidly assess the therapeutic efficacy of strategies for arresting breast cancer at the pre-invasive stage. Since premalignant breast lesions can persist for five years or more before the transition to invasive carcinoma, evaluation of a candidate therapy will require a waiting time of at least five years before the therapeutic efficacy is known. The present invention addresses both of these therapeutic challenges and offers a novel therapeutic target for premalignant breast lesions. SUMMARY In one aspect, there is provided an isolated population of human breast ductal carcinoma in situ (DCIS) cells obtained from a fragment of breast tissue, wherein the cells (i) are epithelial in origin, (ii) comprise one or more markers of autophagy, (iii) show at least one genetic difference from normal cells, (iv) form 3-D spheroids or duct-like structures or ball aggregates and (v) are inhibited in formation of 3-D structures and migration by treatment with chloroquine. In one embodiment, the cells express an increased level of one or more of CD44, COX2 or MMP-14, or a decreased level of CD24 or E-Cadherin compared to monolayer anchorage dependent epithelial cells. In another, the genetic difference is selected from the group consisting of a loss of copy number of 6p21.1 to 6p12.3, a loss of heterozygosity at SUPT3H gene, a gain of copy number at 5p12 to 5p13.3 or a gain of copy number at 17q22 to 17q25.1. In one embodiment, the population comprises the cells of the cell line deposited at ATCC on Mar. 18, 2010 and accorded ATCC No. PTA-10730. In another aspect, methods are provided for making a strain of human breast ductal carcinoma in situ (DCIS) cells from a patient comprising (A) establishing in a container a serum-free organ culture comprising fragments of breast tissue containing stroma, adipose and ductal elements, among which are ductal carcinoma in situ lesions, and (B) allowing the tissue to attach to the container and allowing the DCIS cells to migrate out of the tissue such that the DCIS cells without enzymatic dissociation or immortalization spontaneously form 3-D spherical and ductal tubular structures that contain cells that show at least one genetic difference from normal cells. In addition, methods are provided for assessing whether a potential therapeutic agent is useful for the treatment of pre-neoplastic lesions of the breast comprising administering in vitro the potential therapeutic agent to the population of DCIS cells as described herein, culturing the cells, and determining whether the therapeutic agent inhibits the growth of the cells, proliferation of the cells or tendency of the cells to invade or metastasize. In one, embodiment, the determination step involves evaluating exposed DCIS cells for autophagy, while in another, the determination step involves histomorphologically evaluating exposed DCIS cells. In another aspect, methods of assessing whether a potential therapeutic agent is useful for the treatment of pre-neoplastic lesions of the breast comprise transplanting a population of DCIS cells of claim 1 to a non-human animal model, administering the potential therapeutic agent to the xenotransplant, and determining whether the therapeutic agent inhibits the growth of the cells, proliferation of the cells or tendency of the cells to invade or metastasize. In another, methods of selecting a treatment for a patient with pre-neoplastic lesions of the breast comprise (A) isolating from the patient human breast ductal carcinoma in situ (DCIS) cells as described herein; (B) administering in vitro a potential therapeutic agent to the DCIS cells; (C) culturing the cells; and (D) determining whether the therapeutic agent inhibits the growth of the cells, proliferation of the cells or tendency of the cells to invade or metastasize; and (E) selecting a treatment based upon the determination. In some embodiments, steps (A) to (D) can be repeated after a selected treatment has been administered to the patient. In one aspect, methods of monitoring the efficacy of a treatment of a patient with preneoplastic lesions of the breast, comprise (A) isolating from the patient human breast ductal carcinoma in situ (DCIS) cells as described herein; (B) administering in vitro the potential therapeutic agent to the DCIS cells; (C) culturing the cells; and (D) determining whether the therapeutic agent inhibits the growth of the cells, proliferation of the cells or tendency of the cells to invade or metastasize. In some embodiments, steps (A) to (D) are performed more than once during the course of treatment. In another aspect, methods for preventing or limiting progression of a pre-malignant breast lesion in a patient comprise identifying in the patient a pre-malignant breast lesion and administering to the patient an effective amount of an autophagy inhibitor selected from the group consisting of chloroquine, hydroxychloroquine, 3-methyladenie, clomipramine, ethyl pyruvate and glycyrrhizin. In one embodiment, the autophagy inhibitor is chloroquine. In another, the identification step involves evaluating the lesion for the presence of a DCIS malignant precursor cell (DMPC). In another, the autophagy inhibitor is administered in combination with a chemotherapeutic agent, such as a kinase inhibitor. In some aspects, the kinase inhibitor can be an estrogen modulator, such as tamoxifen, or an aromatase inhibitor. Similarly, methods for treating a pre-malignant breast lesion in a patient comprise identifying in the patient a pre-malignant breast lesion and administering to the patient an effective amount of an autophagy inhibitor selected from the group consisting of chloroquine, hydroxychloroquine, 3-methyladenie, clomipramine, ethyl pyruvate and glycyrrhizin. In one embodiment, the autophagy inhibitor is chloroquine. In another, the identification step involves evaluating the lesion for the presence of a DCIS malignant precursor cell (DMPC). In another, the autophagy inhibitor is administered in combination with a chemotherapeutic agent, such as a kinase inhibitor. In some aspects, the kinase inhibitor can be an estrogen modulator, such as tamoxifen, or an aromatase inhibitor. Other objects, features and advantages will become apparent from the following detailed description. The detailed description and specific examples are given for illustration only since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. Further, the examples demonstrate the principle of the invention and cannot be expected to specifically illustrate the application of this invention to all the examples where it will be obviously useful to those skilled in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 illustrates a tissue culture procedure for growing DCIS organoids that yield epithelial outgrowths for in vitro and in vivo models. FIG. 2A-F shows that human DCIS tissue generates spheroids and pseudoductal structures in ex vivo culture and xenograft neoplasms. (A) H&E stain of human breast DCIS, grade III with comedo necrosis (case 08-352), that represents the primary surgical source material for the organoid culture model system. (B) Human pure DCIS organoids or spheroids transplanted in NOD SCID mice induced tumor formation (arrow) at the mammary fat pad transplantation site within 2 months. (C) H&E stain of murine xenograft tumor (mouse 792, 100×). Note pleomorphic epithelial cells with prominent nucleoli, stromal invasion and partial glandular differentiation. Organoid culture of human DCIS lesions in serum free conditions spontaneously yielded (D) epithelial spheroids (10× magnification) with a single spheroid shown in (E) (40×) and (F) pseudoductal structures with lumen formation (arrow) (40×). FIG. 3A-D show multi-layered growth and invasion of DCIS cultured epithelial cells on autologous breast stroma. DCIS epithelial cells grown from human tissue explants in organoid culture were shown to have neoplastic characteristics as shown by their ability to migrate over the surface of autologous breast stroma, form multi-layered colonies, and invade inward into the stroma. (A) H&E stain of formalin fixed DCIS organoid after 12 weeks in culture. A multi-layered DCIS colony has invaded autologous breast stroma (20×). (B) H&E stain of multi-layered pleomorphic epithelial cells (arrow) on surface of autologous breast stroma after 12 weeks in culture (20×). (C) DCIS cultured neoplastic cell autologous stromal invasion (20×). (D) Example of DCIS multilayered colony on autologous breast stroma in culture for 5 weeks (10×). Cytogenetic analysis of all example cases shown revealed chromosome 6p copy number loss (FIG. 8). FIG. 4 presents bar charts of RPMA characterization of in vitro cell types cultured from human DCIS tissue that confirms structure and function relationship of spheroids (CD44+, COX2+, MMP-14+, E-Cadherin −), epithelial cells (EGFR+, CD44−, ECadherin+), and cuboidal cells (EGFR+, E-Cadherin+). Expanded view of stem cell marker data in lower panel. The activation state of signaling pathways in the DCIS spheroids was compared to the anchorage dependent cells in organoid culture to phenotypically characterize the cell populations. The 48 endpoints analyzed were total or post-translationally modified proteins for a variety of tyrosine kinase receptors and signaling proteins. FIG. 5 schematically demonstrates the proposed paradigm shift in the development of breast cancer, that invasive cells emerge early in the tumorigenesis process. FIG. 6 schematically illustrates the macroautophagy cell signaling pathway. Autophagy (auto—self, phagy—eating) is a catabolic process that can either maintain cellular homeostasis or result in cell death. Intracellular signaling kinases such as AKT, PI3 Kinase, ERK, Bcl-2, and mTOR regulate autophagy. Reverse phase protein microarrays (RPMA) were employed in the present study to evaluate the activation (phosphorylation) of signal pathway proteins that are associated with autophagy. FIG. 7 provides a log R ratio plot showing cultured cells from three different breast DCIS samples that exhibited loss of heterozygosity at a region of chromosome 6p (6p21.1-6p12.3) where the SUPT3H gene is located. FIG. 8 provides a log R ratio plot showing that molecular karyotype of chromosome 6 from human cultured DCIS cells included a deletion p21.1/12.3. The upper panels show the log R ratio plots from 3 different patients (top: 09-148 spheroids/3-D structure; middle: 08-352 3-D structure; bottom: 09-091 spheroids/3-D structure). These data represent DNA ploidy, or copy number, for the displayed chromosomal region with the horizontal wave line indicating the statistical average value. A log R ratio of 0.0 equals a DNA copy number of 2 (diploid). Deflection downward of the line indicates loss of DNA copy number. Each dot represents the log R ratio value for each SNP. The shaded regions represent segments of DNA deviating from a copy number of 2 as determined by the Illumina Genome Studio 2.0 software. The software uses both quantitative fluorescence intensity and qualitative genotypic data for determining copy number values. The center panel shows the chromosomal ideogram indicating cytological bands with the centromere. The small window shows the region expanded in the figure, and the nucleotide positions for this region are shown below the ideogram. The lower panel shows the cytogenetic bands and genetic map for genes located in the expanded region. Note that the region of the deletion for these 3 patients corresponds to the transcript for SUPT3H. FIG. 9 provides a log R ratio plot showing the molecular karotype of chromosome 5 from chloroquine treated or untreated cultured human DCIS cells. Molecular karyotype of chromosome 5 from chloroquine treated cultured DCIS epithelial monolayer and untreated spheroids. The p-arm shows a gain of copy number. The upper panel shows log 2 ratio plots of 2 different samples from the same patient (top: 09-148 chloroquine treated epithelial monolayer; bottom: 09-148 untreated spheroids/3-D structure). In the upper panel, the top plot shows the log R ratio from chloroquine treated human DCIS cell cultures showing normal ploidy, while the lower plot shows a number of extended regions of gain and loss of content on the p-arm of chromosome 5. Details for the legend are listed above. Additional regions of copy number gain are present distally, including subtelomeric regions. The lower panel shows the cytogenetic banding pattern and the corresponding nucleotide positions beginning with the p-telomere. FIG. 10 presents the results of karyotype analysis for human breast DCIS tissue and/or ex vivo cell culture samples. Treated indicates cells were grown in vitro in the presence of Chloroquine 50 mM for >14 days. FIG. 11A-F show that autophagy markers are increased in DCIS and can be inhibited with chloroquine. Immunohistochemistry markers for autophagy endpoints were examined in primary DCIS lesions, mouse xenograft tumors, and DCIS ex vivo generated spheroids/pseudoductal structures. Autophagy markers (Atg5, LC3B, Beclin 1) exhibited prominent positive staining in primary human DCIS lesions (Table 4). (A) IHC of a primary DCIS lesion showing punctate staining within the cytoplasm for LC3B a protein associated with autophagosome formation (anti-LC3B, 100×). (B) Beclin1 positive human DCIS derived mouse xenograft tissue (100×). (C-F) Autophagy is also activated in cultured DCIS pseudoductal structures and spheroids. (C) A bright field image of a multi-cellular pseudoductal structure (20×). (D) Fluorescence microscopy shows accumulation of LysoTracker Red dye within the organelles of the inner cell mass of the structure shown in panel C (20×). (E) LysoTracker Red dye accumulation within the central cell mass of a spheroid (red=LysoTracker Red; blue=DAPI nuclear counterstain, 20×). (F) Chloroquine inhibits autophagy by preventing the fusion of autophagosomes and lysosomes in the dynamic, multi-step autophagy cascade. An organoid culture was maintained in culture medium supplemented with chloroquine phosphate (50 μM) for 2 weeks. Dissociation of the spheroid, and diffuse accumulation of LysoTracker Red in autophagic compartments and Iysosomes were observed (light gray=LysoTracker Red; dark gray=DAPI nuclear counterstain, 20×, Nikon Eclipse TE200 microscope). Note the granular cytoplasm and cellular swelling. FIG. 12A-C show that autophagy markers are present in primary DCIS lesions and DCIS cultured organoids. (A) Case 08-352 surgical specimen is positive for Atg5 staining in comedo DCIS human breast glands (DCIS) compared to adjacent non-neoplastic ductal elements (NL) (10×). (B-C) Enhanced autophagy marker staining persists in organ culture. (B) Positive Atg5 staining of a DCIS organoid after 12 weeks in culture (20×). (C) DCIS organoid in culture showing glandular and stromal elements with positive staining for Beclin 1 (10×) (Hematoxylin counterstain). FIG. 13A-C show that chloroquine suppresses DCIS neoplastic cell outgrowth and spheroid formation and alters cellular signaling. Chloroquine inhibits autophagy by disrupting the autophagosomes/lysosome cascade. A DCIS culture was maintained in DMEM/F12 culture medium supplemented with EGF, insulin, gentamicin and streptomycin. After epithelial cells and spheroids formed in culture, the medium was treated with chloroquine phosphate (50 μM) for 4 days. Spheroids were harvested pre and post chloroquine treatment. (A) Chloroquine markedly inhibited autophagy associated pathways as shown by a reduction in autophagy pathway proteins (Atg5, AKT Ser473, AKT Thr308, APMKβ1 Ser108, ERK Thr202/Tyr204, mTOR Ser2448), adhesion proteins (Laminin5, Integrin α5β1), and proliferation/survival proteins (Musashi, Bad Ser136, c-RAF Ser338, GSK3α/β, Ser21/9, IRS-1 Ser612, Survivin, FOX01/03 Thr24/32, Grb2, c-RAF Ser338, Met Tyr1234/1235, p38 MAPK Thr1801Tyr182, PTEN Ser380) (n=3, ±SEM). (B) Chloroquine suppressed outgrowth of DCIS epithelial cells in culture as measured by the diameter of the outgrowth. Two axis diameters were measured for multiple organoids for two cases. The mean diameter of case 09-148-A outgrowth prior to treatment (open circle) was 0.85 cm±0.11 (n=15, mean±SEM) and after chloroquine treatment (black circle), the mean diameter was 0.084 cm±0.03 (n=23, mean±SEM) (p<0.0001). In the second series of organoid cultures, the mean diameter of case 09-148-B outgrowth prior to treatment (open triangle) was 1.36±0.25 (n=8, mean±SEM) while the chloroquine treated outgrowth (black triangle) mean diameter was 0.21±0.03 (n=7, mean±SEM) (p=0.0026). (C) The number of spheroids generated in the untreated cultures (open circle, case 09-148) ranged from 1 to more than 100 for individual duct fragments (mean of 38.7±11; n=14, mean±SEM). Following chloroquine treatment, 12 out of 14 explants did not have any spheroids (mean number of spheroids post treatment 0.21±0.15; n=14; p=0.0049, black circle, mean±SEM). For case 09-301, the mean number of spheroids prior to treatment was 20.5±7.8, n=14 (open triangle, mean±SEM) and there were no spheroids observed after treatment (n=3; black triangle, mean±SEM). FIG. 14A-D show chloroquine treatment of DCIS organoid cell cultures is associated with cellular degeneration and necrosis. Human breast ductal tissue was allowed to attach to the culture surface and grow in culture for at least 4 weeks prior to treatment with medium containing chloroquine phosphate (50 μM). (A) Degeneration of the invading DCIS cells within the organoid 2 days post chloroquine treatment (10×). (B) DCIS organoid cultured in the presence of chloroquine for 6 months showed complete absence of cellular outgrowths and degenerated cells within the duct (arrow) (10×). (C) Degeneration (arrow) of the multi-layered autologous stromal colony can be compared to the untreated multi-layered growth in FIGS. 3B & D (10×). (D) Cellular swelling and apparent apoptotic death (arrow) of DCIS intraductal epithelial cells within organoid DCIS ductal lesions. (20×) H&E stain of FFPE tissue sections. FIG. 15A-B show sub-cellular localization of SUPT3H by immunohistochemistry staining. The SUPT3H gene, located on chromosome 6p in region p21.1 to p12.3, was deleted in the DCIS derived spheroids of three different patients (see FIG. 8). FFPE tissue sections from samples of DCIS with central necrosis were stained with anti-SUPT3H to explore the cell localization of this putative transcription factor in DCIS. Staining is noted in the peri-nuclear membrane zone, as shown by outlining of the nuclei, for a subset of intraductal cells. (A) Case 08-183. (B) Case 08-352, (20×). DETAILED DESCRIPTION Progenitor cancer cells have been discovered in human breast ductal carcinoma in situ (DCIS) lesions. The DCIS malignant precursor cells (DMPC) were isolated from the fresh living human DCIS lesions and propagated into cell strains. These cells are characterized by a) invasive growth b) formation of 3-Dimensional spherical or tubular structures without enzymatic treatment or requirement for a collagen gel growth medium, and c) cytogenetic abnormalities distinct from the normal cells of the patient donor. The cells are useful in drug design and drug screening. In addition, isolated DMPC from a patient can be used to evaluate and monitor the efficacy of potential therapies. The DCIS cells are shown to be dependent on cellular autophagy for survival, and inhibition of autophagy suppresses or destroys the DCIS cells. Thus, in another aspect, methods of treating, or limiting the progression of, pre-malignant breast lesions are provided. DEFINITIONS As used herein, the term “lesion” refers to any abnormal tissue found on or in an organism, usually damaged by disease or trauma. A lesion can be a cancer or precancerous tissue which can be isolated by surgical procedure, for example, biopsy. As used herein, the term “preneoplastic” refers to a tumorigenesis stage preceding the formation of a benign or malignant neoplasm. “Neoplasm”, as used herein, refers to an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of this clone of cells can exceed, and can be uncoordinated with, that of the normal tissues around it. It usually causes a lump or tumor. Neoplasms can be benign, pre-malignant or malignant. The term “pre-neoplastic lesion”, as used herein, refers to a lesion of pre-neoplastic stage. A “population” of cells intends a collection of more than one cell that is identical (clonal) or non-identical in phenotype and/or genotype. As used herein, the term “propagate” means to grow or cultivate a population of cells. The term “growing” refers to the proliferation of cells in the presence of supporting media, nutrients, growth factors, support cells, or any chemical or biological compound necessary for obtaining the desired number of cells or cell type. In one embodiment, the growing of cells results in the regeneration of tissue. As used herein, the term “culturing” refers to the in vitro propagation of cells or organisms on or in media of various kinds. It is understood that the descendants of a cell grown in culture may not be completely identical (i.e., morphologically, genetically, or phenotypically) to the parent cell. By “expanded” is meant any proliferation or division of cells. As used herein, the “lineage” of a cell defines the heredity of the cell, i.e. its predecessors and progeny. The lineage of a cell places the cell within a hereditary scheme of development and differentiation. As used herein, the term “CD44” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human CD44 sequence of GenBank Accession No. NP—000601. Suitable cDNA encoding CD44 is provided at GenBank Accession No. NM—00061. “CD44” is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. CD44 has been reported as cell a surface marker for breast and prostate cancer stem cells. As used herein, the term “COX2”, “Prostaglandin-endoperoxide synthase (PTGS)” or “cyclooxygenase” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human COX2 sequence of GenBank Accession No. NP—000954. Suitable cDNA encoding COX2 is provided at GenBank Accession No. NM—000963. “COX2” is a key enzyme in prostaglandin biosynthesis, which acts both as a dioxygenase and as a peroxidase. COX2 is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. As used herein, the term “MMP-14”, or “matrix metallopeptidase 14” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human MMP-14 sequence of GenBank Accession No. NP—004986. Suitable cDNA encoding MMP-14 is provided at GenBank Accession No. NM—004995. MMP-14 a protein of the matrix metalloproteinase (MMP) family that is involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion. Representative GenBank Accession Numbers for MMP-14 include NP—004986 for protein and NM—004995 for nucleotide sequences. As used herein, the term “CD24” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human CD24 sequence of GenBank Accession No. NP—037362. Suitable cDNA encoding CD24 is provided at GenBank Accession No. NM—013230. As used herein, the term “E-cadherin” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human E-cadherin sequence of GenBank Accession No. NP—004351. Suitable cDNA encoding E-cadherin is provided at GenBank Accession No. NM—004360. E-cadherin is from the cadherin superfamily. The encoded protein is a calcium dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function is thought to contribute to progression in cancer by increasing proliferation, invasion, and/or metastasis. As used herein, the term “SUPT3H”, “transcription initiation protein SPT3 homolog” or “suppressor of Ty 3 homolog” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human SUPT3H sequence of GenBank Accession No. NP—003590. Suitable cDNA encoding SUPT3H is provided at GenBank Accession No. NM—003599. In one embodiment, the present disclosure provides a loss of heterozygosity (LOH) that is narrowly confined to a region of chromosome 6p (6p21.1-6p12.3) that contains one gene, SUPT3H. This LOH is associated with the human breast ductal carcinoma in situ (DCIS) progenitor cell phenotype. Breast DCIS cells with this abnormal phenotype (i.e. exhibiting the LOH) are prevented from forming out growths (ex vivo) in the presence of Chloroquine (50 mM). Since this genetic alteration is a LOH it implies a suppressor function for the protein product of this gene. Consequently the protein product of this gene is a potential therapeutic target for preventing DCIS and/or invasive breast carcinoma. Restoring the missing function of this gene could be a therapy for preventing DCIS and/or invasive breast cancer. Thus, SUPT3H could be used as a new prognostic/diagnostic marker or method for selecting human breast DCIS cells with invasive potential. The treatment target is the autophagy pathway, and an exemplary treatment agent is chloroquine, which could be used for chemoprevention. The term “autophagy” or “autophagocytosis”, as used herein, refers to a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly-regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products. It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more-essential processes. A variety of autophagic processes exist, all having in common the degradation of intracellular components via the lysosome. Markers, or “autophagy markers”, are known in the art to identify the occurrence of the autophagy process in a cell. Non-limiting examples of autophagy markers include LC3B, Atg5, Beclin-1, mTOR, and phosphorylation of Akt on serine 473. As used herein, the term “LC3B”, “MAP1LC3B” or “microtubule-associated protein 1 light chain 3 beta” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human LC3B sequence of GenBank Accession No. NP—073729. Suitable cDNA encoding LC3B is provided at GenBank Accession No. NM—022818. LC3B is a subunit of neuronal microtubule-associated MAP1A and MAP1B proteins, which are involved in microtubule assembly and important for neurogenesis. Research in rat has shown a role for this gene in autophagy, a process that involves the bulk degradation of cytoplasmic component. As used herein, the term “Atg5”, or “microtubule ATG5 autophagy related 5 homolog” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human Atg5 sequence of GenBank Accession No. NP—004840. Suitable cDNA encoding Atg5 is provided at GenBank Accession No. NM—004849. As used herein, the term “Beclin-1”, “BECN1” or “beclin 1, autophagy related” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human Beclin-1 sequence of GenBank Accession No. NP—003757. Suitable cDNA encoding Beclin-1 is provided at GenBank Accession No. NM—003766. As used herein, the term “mTOR”, or “mechanistic target of rapamycin” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human Beclin-1 sequence of GenBank Accession No. NP—004949. Suitable cDNA encoding Beclin-1 is provided at GenBank Accession No. 1.NM—004958. The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. As used herein, the term “Akt”, “Aktl” or “v-akt murine thymoma viral oncogene homolog” refers to a protein having an amino acid sequence substantially identical to, or a mammalian protein homologue or isoform of, the human LC3B sequence of GenBank Accession No. NP—001014431. Suitable cDNA encoding LC3B is provided at GenBank Accession No. NM—001014431. AKT is a mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT, which then phosphorylates and inactivates components of the apoptotic machinery. As used herein, the term “epithelial membrane antigen” or “EMA” refers to an antigen expressed on the surface of an epithelial cell. EMA belongs to a heterogeneous family of highly-glycosylated transmembrane proteins known as human milk fat globule (HMFG) membrane proteins. This family of antigens is not restricted to breast but may also be found in secretory epithelial cells, to a lesser degree, in nonsecretory epithelium (e.g., squamous epithelium) and rarely in nonepithelial cells. A non-limiting example of EMA is Epithelial cell adhesion molecule (EpCAM), a protein that in humans is encoded by the EPCAM gene. A representative mRNA sequence is GeneBank Accession No. NM 002354, and protein sequence is GeneBank Accession No. NP—002345. As used herein, the term “chloroquine” refers to N′-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine. A “chemical equivalent of chloroquine”, as used herein, refers to a 4-aminoquinoline that is structurally similar to chloroquine and/or has anti-malarial or anti-autophagy activity. DCIS Malignant Precursor Cells In one aspect, an isolated living human breast ductal carcinoma in situ (DCIS) malignant precursor cell is provided. In one embodiment, the DCIS malignant precursor cell is potentially malignant or invasive. In another embodiment, the DCIS malignant precursor cell is cytogenetically abnormal. In yet another embodiment, the DCIS malignant precursor cell requires cellular autophagy for survival. In one embodiment the malignant or invasive potential of the DCIS malignant precursor cell can be identified by the cell's anchorage independent growth and migration or ability to form 3-D structures. Non-limiting examples of 3-D structures include spheroids, duct-like structures, tube-like structures, epithelial or cuboidal cobblestone sheets or differentiated structures. The malignant or invasive potential of the DCIS malignant precursor cell can further or alternatively be identified by the cell's ability to be propagated without exogenous immortalization. In one aspect, the DCIS malignant precursor cell can be propagated for at least about a month, or alternatively at least about two, about three, about six, about 12 or about 24 months. In another aspect, the DCIS malignant precursor cell can be propagated for at least about 10 passages, or alternatively for at least about 20 passages, about 30 passages, about 50 passages or about 100 passages. The malignant or invasive potential of the DCIS malignant precursor cell can further or alternatively be identified by the cell's ability to invade autologous stroma in organ culture. The malignant or invasive potential of the DCIS malignant precursor cell can further or alternatively be identified by the cell's ability to generate tumors when transplanted into NOD SCID mice. In one aspect, the tumors can be observed at about a month after transplantation. In another aspect, the tumors can be observed at about two months after transplantation. In yet another aspect, the tumors can be observed at between one month and six months after transplantation. In another embodiment, the DCIS malignant precursor cell is cytogenetically abnormal. Non-limiting examples of cytogenetic abnormality include loss or gain of chromosome copy numbers, such as loss of copy number on chromosome 5, 6, 8 or 13 or gain of copy number on chromosome 1, 5 and 17. In one aspect, the cytogenetic abnormality is loss of chromosome or loss of heterozygosity of chromosome 6 (p21.1/p12.3). In another aspect, the cytogenetic abnormality is loss of heterozygosity of the SUPT3H gene. In yet another aspect, the cytogenetic abnormality is gain of copy number of 5p12 to 5p13.3. In another aspect, the cytogenetic abnormality is gain of copy number of 17q22 to 17q25.1. In yet another embodiment, the DCIS malignant precursor cell requires cellular autophagy for survival. In one aspect, therefore, the DCIS malignant precursor cell can be identified by one or more autophagy markers. Non-limiting examples of autophagy markers include LC3B, Atg5, Beclin-1, mTOR, and phosphorylation of Akt on serine 473. Accordingly, an increased expression of LC3B, Atg5, Beclin-1 or mTOR in the DCIS cell, or an increased phosphorylation of Akt on serine 473 identifies the DCIS cell as a DCIS malignant precursor cell. The increase of expression or phosphorylation of the autophagy markers, in some embodiments, can be at least about 10%, about 20%, about 30%, about 50%, about 100%, about 150%, about 2 folds, about 3 folds, about 5 folds, about 10 folds, or about 20 folds of the expression of the corresponding marker in a suitable control sample. A suitable control sample can be a normal breast stroma cell or tissue. In another aspect, the DCIS malignant precursor cell can further or alternatively be identified by the inhibition of its growth, migration or invasion by an autophagy inhibitor. Non-limiting examples of autophagy inhibitors include chloroquine, 4-aminoquinoline or a chemical equivalent thereof. In a particular aspect, the formation of 3-D structures by the DCIS malignant precursor cells can be inhibited by contacting the cell with chloroquine, a 4-aminoquinoline or a chemical equivalent thereof. In some embodiments, the provided DCIS malignant precursor cell has high or increased expression of CD44, COX2 and MMP-14, or low or decreased expression of CD24 or E-Cadherin, as compared to a suitable control sample, such as a duct epithelial cell that is not neoplastic. The increase of expression of the cell surface markers, in some embodiments, can be at least about 10%, about 20%, about 30%, about 50%, about 100%, about 150%, about 2 folds, about 3 folds, about 5 folds, about 10 folds, or about 20 folds of the expression of the corresponding marker in the suitable control sample. The decrease of expression of the cell surface markers, in some embodiments, can be at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90% or about 95% of the expression of the corresponding marker in the suitable control sample. In another aspect, DCIS malignant precursor cells can exhibit signal pathway activation of prosurvival, autophagy, cell migration, cell adhesion, hypoxia, genetic instability, proteosome, or stem cell related pathways. In some embodiments, the DCIS malignant precursor cell is of epithelial origin. The epithelial origin of the DCIS malignant precursor cell can be tested with an epithelial membrane antigen (EMA) such as the epithelial cell adhesion molecule (EpCAM). In one embodiment, an isolated population of human breast ductal carcinoma in situ (DCIS) cells obtained from a fragment of breast tissue is provided, wherein the cells (i) are epithelial in origin, (ii) are positive for markers of autophagy, (iii) show at least one genetic difference from normal cells, (iv) form 3-D spheroids or duct-like structures or ball aggregates and (v) are inhibited in formation of 3-D structures and migration by treatment with chloroquine, a 4-aminoquinoline or a chemical equivalent thereof. Distinguishing Genetic Features DCIS malignant precursor cells are cytogenetically abnormal compared to normal or non-neoplastic cells. The DCIS malignant precursor cells can display a loss of heterozygosity (LOH) in a narrowly confined region of chromosome 6p (6p21.1-6p12.3) that contains the gene SUPT3H (Transcription initiation protein SPT3 homolog). Thus, in one embodiment, the DCIS malignant precursor cells can be identified by a LOH in SUPT3H. Other non-limiting examples of cytogenetic abnormality include loss or gain of chromosome copy numbers, such as loss of copy number on chromosome 5, 6, 8 or 13 or gain of copy number on chromosome 1, 5 and 17. In one aspect, the cytogenetic abnormality is gain of copy number of 5p12 to 5p13.3. In another aspect, the cytogenetic abnormality is gain of copy number of 17q22 to 17q25.1. In another aspect, the DCIS progenitor cells comprise the cells of the cell line deposited with the American Type Culture Collection, P.O. Box 1549, Manassas, Va., USA, 2010 on Mar. 18, 2010 and accorded ATCC Accession No. PTA-10730. Methods of Making In another aspect, a method for preparing an isolated malignant precursor human breast ductal carcinoma in situ (DCIS) cell or a strain of such cells from a patient comprises (A) establishing in a container a serum-free organ culture comprising fragments of breast tissue containing stroma, adipose and ductal elements, which include ductal carcinoma in situ (DCIS) lesions, and (B) allowing the tissue to attach to the container and the DCIS cells to migrate out of the tissue and spontaneously form 3-D spheroids and tubular structures in serum free media without enzymatic dissociation and migrate on the surface of autologous breast stroma (FIGS. 1-3). In one embodiment, the DCIS cells migrating on the autologous stroma invade the stroma. In another, the morphology of the DCIS ductal lesion in the fragment of human breast tissue is maintained for at least 6 weeks. The breast lesions can be rinsed with a buffer, such as phosphate buffered saline (PBS), prior to culturing. The buffer may contain antibiotic and/or anti-fungal agents such as, but not limited to gentamicin and streptomycin. The lesions then can be minced into small pieces and suspended in dissociation media. The dissociation media can be basal media supplemented with a cell dissociation agent, such as but not limited to EDTA, EGTA, trypsin and collagenase-dispase. The dissociated cells or cell aggregates then can be pelleted by centrifugation and resuspended in basal medium, and transferred to a culture dish. In one embodiment, the breast lesions can be rinsed in a variety of basal media, prior to culturing. The basal medium may contain antibiotic and/or anti-fungal agents such as, but not limited to, gentamycin and streptomycin. The lesions then can be minced into small pieces and cultured directly in a culture dish without dissociation. A wide variety of basal media can be used to keep the pH of the liquid in a range that promotes survival of DCIS malignant precursor cells. Non-limiting examples include F12/DMEM, Ham's F10 (Sigma), CMRL-1066, Minimal essential medium (MEM, Sigma), RPMI-1640 (Sigma), Dulbecco's Modified Eagle's Medium (DMEM, Sigma), OPTI-MEM® (GIBCO BRL) and Iscove's Modified Eagle's Medium (IMEM). In one embodiment, nutrients can be added to supplement the basal medium. In another, growth factors or hormones can be added to supplement the basal medium, such as, but not limited to, EGF, insulin and estrogen. DCIS malignant precursor cells can migrate out of the cell aggregates into the medium and anchor to the culture dish or other supplied anchor material. The remnant of the minced tissues that do not attach to the culture dish or anchor will flow in the medium and will be removed by medium change. In another embodiment, cells from the cell aggregates placed in media all attach to the culture dish and the DCIS malignant precursor cells can slowly establish and grow among the other cell types. Eventually, the DCIS malignant precursor cells will form a substantially pure population of cells and the other cell types will no longer be in the culture. The culture process and environment will not support the replication and/or survival of contaminating cell types and will promote the survival and growth of the human cancer stem cells so as to generate a substantially pure population of DCIS malignant precursor cells growing as 3-D structures such as spheroids (FIGS. 1-3). Screening Methods In another aspect, a method of assessing whether a potential therapeutic agent is useful for the treatment of pre-neoplastic lesions of the breast comprises administering in vitro the potential therapeutic agent to a population of the DCIS malignant precursor cells of any of the above embodiments, culturing the cells, and determining whether the therapeutic agent inhibits the growth of the cells, proliferation of the cells or tendency of the cells to invade or to metastasize. The determination step can involve assessment of reversal of the invasive or progenitor characteristics of the DCIS malignant precursor cells as described supra. In one embodiment, inhibition of growth or proliferation of the DCIS malignant precursor cells can be determined by counting the number of cells following treatment with a potential therapeutic agent, as compared to untreated cells (FIGS. 13, 14). In another embodiment, the DCIS cells' progenitor potential can be determined by transplanting the cells into a non-human animal as described below. In another aspect, a method of assessing whether a potential therapeutic agent is useful for the treatment of pre-neoplastic lesions of the breast comprises transplanting a population of DCIS cells of any of the above embodiments to a non-human animal model, administering the potential therapeutic agent to the xenotransplant, and determining whether the therapeutic agent inhibits the growth of the cells, proliferation of the cells or tendency of the cells to grow as tumors, invade or metastasize. In one embodiment, the potential therapeutic agent may be combined with other substances such as anti-estrogen agents, estrogen binding inhibitors, or estrogen activity inhibitors. In another, the tendency of the DCIS malignant precursor cells can be determined by examining formed tumors in the non-human animal after a period of time, such as 12 or 24 months, after transplantation. The determination can include a group of non-human animals, each of which is transplanted with an equal size subpopulation of the DCIS malignant precursor cell population, treated or not treated with the potential therapeutic agent. No tumor formulation or a reduced number of tumor formation derived from the transplants indicates that the potential therapeutic agent is useful for the treatment of the pre-neoplastic lesion. Treatments In another aspect, methods are provided for preventing or limiting progression of a pre-malignant breast lesion in a patient. Such methods comprise administering to the patient an effective amount of an autophagy inhibitor. In another, methods are provided for treating a patient comprising a pre-malignant breast lesion, comprising administering to the patient an effective amount of an autophagy inhibitor. The pre-malignant breast lesions can comprise a ductal carcinoma in situ (DCIS) malignant precursor cell or an atypical ductal hyperplasia cell. An autophagy inhibitor refers to any chemical or biological agent that inhibits the activity or suppresses the expression of a gene that positively regulates the autophagy pathway such as, but not limited to, Beclin-1, Atg5, Atg7 or Atg8, or activates the activity or increases the expression of a gent that negatively regulates the autophagy pathway. Non-limiting examples of autophagy inhibitors include chloroquine, hydroxychloroquine, 3-methyladenie, clomipramine, ethyl pyruvate, glycyrrhizin, an agent decreasing the biological activity of one or more of Beclin-1, Atg5, Atg7 or Atg8 and combinations thereof. In one embodiment, the autophagy inhibitor is chloroquine. The autophagy inhibitors can used alone or in combination with a chemotherapeutic agent. A variety of chemotherapeutic agents are known in the art. Examples include, but are not limited to, cyclophosphamide, doxorubicin, docetaxel, methotrexate, fluorouracil, trastuzumab, tamoxifen, toremifene citrate, lapatinib, axitinib, or pazopanib. In one aspect, the chemotherapeutic agent is a kinase inhibitor. A variety of kinase inhibitors are known in the art. Examples include, but are not limited to, tamoxifen, toremifene citrate, lapatinib, axitinib, or pazopanib. In one embodiment, the kinase inhibitor is tamoxifen. Treatment Selection In another aspect, a method of screening the efficacy of a treatment or selecting a treatment for pre-neoplastic lesions of the breast comprises (A) isolating human breast ductal carcinoma in situ (DCIS) cells from the patient with a method disclosed herein; (B) administering in vitro the potential therapeutic agent to the DCIS cells; (C) culturing the cells; and (D) determining whether the therapeutic agent inhibits the growth of the cells, proliferation of the cells or tendency of the cells to metastasize; and (E) selecting a treatment based upon the determination. In some embodiments, steps (A) to (D) can be repeated after a selected treatment has been administered to the patient. In one embodiment, the potential treatment agent may be combined with other substances such as anti-estrogen agents, estrogen binding inhibitors, or estrogen activity inhibitors. Treatment Monitoring In another aspect, a method of monitoring the efficacy of a treatment of a patient with pre-neoplastic lesions of the breast comprises (A) isolating human breast ductal carcinoma in situ (DCIS) cells from the patient with a method disclosed herein; (B) administering in vitro the potential therapeutic agent to the DCIS cells; (C) culturing the cells; and (D) determining whether the therapeutic agent inhibits the growth of the cells, proliferation of the cells or tendency of the cells to invade or grow as tumors. In some embodiments, steps (A) to (D) are performed more than once during the course of treatment. In one embodiment, the determining step comprises examining the cells in culture conditions, or alternatively by transplanting the cells into a non-human animal to examine the cells' potential to grow, proliferate and metastasize, as described supra. In one embodiment, the potential therapeutic agent may be combined with other substances such as anti-estrogen agents, estrogen binding inhibitors, or estrogen activity inhibitors. Embodiments will be further described in the following non-limiting examples. EXAMPLES Example 1 Malignant and Invasive Cancer Cells from DCIS Lesions It has been discovered that human living DCIS lesions contain cells with the ability to grow as invasive tumors in mouse xenografts. Tumor Transplantation: Breast ductal tissue was incubated with EGF, insulin, and Estrogen in RPMI1640 for 4-12 hours prior to transplantation into the mammary fat pad of NOD/SCID mice (Jackson Labs/Harlan). Tumors that appeared within 2 months of transplantation were excised (Table 1). A portion was saved for in vitro cultivation and the remainder was transplanted for propagation and phenotype analysis. Results TABLE 1 Breast xenograft characteristics and tumor generation. Xenograft Mouse ID Tissue type ER PR Her2 Tumor 793 Breast normal no 395 DCIS yes 398 DCIS yes 581 DCIS yes 876 DCIS yes 079 DCIS Pos (50%) Pos (50%) yes 080 DCIS Pos (50%) Pos (50%) yes 081 DCIS Pos (50%) Pos (50%) yes 082 DCIS Pos (50%) Pos (50%) yes 379/579 DCIS yes 396 DCIS yes 783/763 DCIS Pos (50%) Pos (50%) yes 791 DCIS yes 792 DCIS Pos (>90%) Pos (>90%) yes 794 DCIS no 795 DCIS no 528 DCIS Cell Culture Pos (50%) Pos (50%) pending 530 DCIS Cell Culture Pos (50%) Pos (50%) pending 631 DCIS Cell Culture Pos (50%) Pos (50%) yes 632 DCIS Cell Culture Pos (50%) Pos (50%) yes 633 DCIS Cell Culture Pos (50%) Pos (50%) yes 634 DCIS Cell Culture Pos (50%) Pos (50%) yes 635 DCIS Cell Culture Pos (50%) Pos (50%) yes 684 DCIS Cell Culture Pos (50%) Pos (50%) yes 686 DCIS Cell Culture Pos (50%) Pos (50%) no 687 DCIS Cell Culture Pos (50%) Pos (50%) no 054 DCIS pure Pos (85%) Neg yes 055 DCIS pure Pos (>90%) Pos (30%) yes 101 DCIS pure Pos (30%) Neg yes 102 Infiltrating DCIS no 103 Infiltrating DCIS yes 306 Infiltrating DCIS no 307 Infiltrating DCIS yes 308 Infiltrating DCIS no 309 Infiltrating DCIS no 310 Infiltrating DCIS no 399 Infiltrating DCIS 3.6 no 964 Infiltrating DCIS no 965 Infiltrating DCIS no 396 Invasive DCIS yes 301 Lobular no 962 Lobular yes 963 Lobular no 961 Lobular invasive no 877 propagated xenograft DCIS Pos (30%) Neg yes 051 propagated xenograft DCIS yes 391 propagated xenograft DCIS yes 392 propagated xenograft DCIS yes 395 propagated xenograft DCIS with yes IDC 393 propagated xenograft IDC no 394 propagated xenograft pure DCIS yes 311 Xenograft culture no Live ductal tissue from nine DCIS lesions were transplanted into NOD/SOD mice. The following aspects were observed: Number of DCIS/IDC cases transplanted: 18 with 43 pieces of tissue transplanted; Number of tumors generated within 3 months: 23; Number of tumors observed for pure DCIS tissue: 18; Tumors observed for mixed DCIS IDC tissue n=5; 7 xenograft propagations yielded 5 tumors for 2 generations from tumor lines derived from pure DCIS. 5/7 xenograft tumors were produced from a primary DCIS tissue cell strain that was in culture for 1-2 months. Example 2 DCIS Cells Propagated In Vitro No information exists concerning the existence of tumorigenic/malignant precursor cells within living human pre-invasive lesions such as Ductal Carcinoma in situ (DCIS). It has been discovered, however, that malignant precursor cells exist in DCIS lesions and can propagate in vitro and in vivo (FIGS. 1-4). Methods Reverse Phase Protein Array Analysis. Human DCIS breast cells were cultured in minimal medium supplemented with EGF and Insulin in the presence of Streptomycin and Gentamicin. Cells with distinct morphologies were removed by aspiration and mechanical disruption (scraping), spun at 1000 rpm for 5 min, medium was removed and the cell pellet was lysed in TPER, 2× Tris-glycine sample buffer with 10% TCEP Bond Breaker. Reverse phase protein microarrays were printed with an Aushon 2470 arrayer. Staining and Analysis. Slides were stained with 65 antibodies against phosphorylated proteins involved in pro-survival, growth regulation and apoptosis signaling; antibody binding was visualized using the Catalyzed Signal
{'application_number': '<application-reference appl-type="utility">\n<document-id>\n<country>US</country>\n<doc-number>12914830</doc-number>\n<date>20101028</date>\n</document-id>\n</application-reference>', 'publication_number': '<publication-reference>\n<document-id>\n<country>US</country>\n<doc-number>20110104065</doc-number>\n<kind>A1</kind>\n<date>20110505</date>\n</document-id>\n</publication-reference>', 'source_file': './application/2011/ipa110505.xml', 'source_data': 'USPTO-Application'}