aapko basic science video topic breast
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disorders breast disease encompasses a
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wide spectrum of disorders that range
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from benign to malignant disease the
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different ideologies of breast disease
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fluctuate depending on a patient’s age
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with benign disorders more common in
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premenopausal women and malignancy more
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common in older patients the objectives
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of this video include understand normal
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breast anatomy and histology identify
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common benign breast disorders and
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breast cancer and describe the mechanism
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of action for hormonal therapies used in
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breast cancer treatment to review the
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clinical aspects and management of
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breast disorders please see the aapko
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educational topic number 40 on disorders
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of the breast let’s meet our patient
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she’s a 50 year old who presents to
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clinic for routine GYN exam
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she has no particular concerns but would
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like a referral for screening mammogram
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before you do her exam let’s review the
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normal anatomy and histology of the
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breasts breast tissue is composed of
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both stromal and epithelial tissue the
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stromal tissues comprise the majority of
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breast volume and include adipose and
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fibrous connective tissue the epithelial
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tissue is a ductal system which
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transports milk from the lobules to the
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nipple each breast has about 12 to 20
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lobes let’s zoom in each low of consists
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of lobules which is drawn here
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they consist of alveoli or SNI sac-like
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structures where milk is synthesized and
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secreted the lobules drain into a
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terminal duct the lobules and the
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terminal duct in which they drain is
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known as the terminal duct lobular unit
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or TDL you remember this term as it will
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come up again later the ducts are
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surrounded by myoepithelial cells to
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allow for milk ejection let’s take a
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look at normal histology in this image
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you can see a TDL you with both lobules
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and the duct in higher power with a
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special scene myoepithelial cells are
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brown and surround the inner ring of
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ductal cells the terminal ducts then
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drain into larger collecting ducts prior
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to the nipple there is a dilation of the
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duct known as electa for a sinus which
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then opens to the nipple there are about
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six days openings to the nipple let’s go
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back to our patient her breast exam is
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normal and no suspicious masses are
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palpated you order a mammogram a couple
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days later her is
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come back there’s an abnormal area seen
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on the mammogram and biopsy is
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recommended she is nervous and would
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like to know of its cancer you discuss
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with her the possibility of benign
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versus malignant disease let’s start by
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reviewing benign breast disorders they
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are classified histologically into three
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categories non-proliferation
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proliferative without a tibia in a
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typical hyperplasia the risk of
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developing breast cancer increases as we
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move to the right non proliferative
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disorders are generally not associated
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with increased risk of breast cancer and
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include breast cysts and fibrocystic
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change breast cysts are most common in
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women between the ages of 35 to 50 they
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are fluid-filled and round or ovoid in
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shape fibrocystic change is very common
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in reproductive age women and can cause
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cyclic pain in palpably nodular tissue
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what does it look like under the
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microscope on the left is a normal t dlu
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and on the right is fibrocystic change
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with fibrocystic change there is
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dilation of sni and ducts with dense
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stroma proliferative without atypia
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disorders increase the risk of
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developing breast cancer by 1.5 to 2
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they include intraductal papillary
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adenoma unusual ductal hyperplasia
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intraductal papillary present with
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Sarris or bloody nipple discharge they
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are most commonly found less than 2
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centimeters from the nipple if this is a
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duct wall imagine a broccoli stalk
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shaped growth inside the duct they are
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the proliferation of epithelial cells
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within the ducts appearing as fronds and
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attached to the inner wall of the duct
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with a central fiber vascular stalk
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surgical excision is generally
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recommended fibroadenomas are common
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from age 15 to 35 and present as a
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well-defined mobile mass they generally
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do not increase the risk of cancer but
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can slightly increased risk such as if
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they have complex features
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microscopically there’s a dense stromal
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component with compressed ducts you can
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see a sharp interface with normal breast
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tissue which makes the mass well
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circumscribed fibroadenomas can be
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observed or be surgically excised usual
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ductal hyperplasia and retained
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psychological features of benign cells
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no additional treatment is needed
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microscopically there are increased
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cells in parts of the duct the last
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category and benign breast disorders is
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atypical hyperplasia these disorders
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increase the risk of subsequent breast
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cancer with a relative risk of 3.7 to
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5.3 and include atypical ductal
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hyperplasia or ADH atypical lobular
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hyperplasia or a LH and often includes
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lobular carcinoma in situ or LCIS but
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note that the relative risk of breast
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cancer is different
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LCIS is associated with a 7 to 10 times
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increased relative risk of breast cancer
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ADH is similar to low grade DCIS which
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we will discuss later in this video but
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is a less extensive lesion measuring
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less than 0.2 centimeters is the
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proliferation of low-grade neoplastic
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ductal epithelial cells filling part but
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not the entire involved duct surgical
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excision is generally recommended as
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rates of pathology can be upgraded to
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more severe disease in 10 to 20 percent
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of cases atypical lobular hyperplasia is
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similar to LCIS but with less extensive
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disease proliferation of low-grade
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neoplastic cells feel less than 50% of
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Vasa Knight in an involved lobule with
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slight distension since the rate of
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upgrade of pathology is low less than 5%
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treatment can be observation let’s
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compare a lh2 lobular carcinoma in situ
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or LCIS as noted previously
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LCIS is associated with a 7 to 10 times
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increase relative risk of breast cancer
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it has greater extent of disease than
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alh with increased S&I distension in the
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majority of cases nuclear grade is low
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in this histopathology image you can see
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LCAs compared to a benign TDL you
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zooming in you can see intraductal
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proliferation of cells that are fairly
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homogeneous and are loosely arranged or
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disco hee Civ LCIS is poorly understood
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and is not clear how it directly leads
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to breast cancer like alh treatment is
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typically close observation rather than
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surgery our patients biopsy comes back
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as ductal carcinoma in situ or DCIS
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sometimes referred to as stage zero
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cancer this is typically diagnosed after
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there are micro calcifications on
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mammogram as seen in this image cancer
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cells fill the ductal system without
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beyond the basement membrane unlike in
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LCIS the cells are cohesive in this
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image cells are low nuclear grade in
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cells are homogeneous this image
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demonstrates a higher grade DCIS lesion
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there’s variability in size of the cells
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and prominent nucleoli comedo necrosis
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is when there’s a necrotic core in the
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center of a duct filled with cancer
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cells high nuclear grading and presence
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of comedone acrosses increases the
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recurrence risk of DCIS or invasive
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disease treatment is surgical excision
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when found on core biopsy 10 to 20% of
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patients will have an invasive cancer
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and subsequent excision let’s discuss
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invasive breast cancers prognosis and
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treatment decisions are based on hormone
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receptor status nuclear grade and her2
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new expression her2 new is a type of
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receptor tyrosine kinase that promotes
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the growth of cancer cells and is
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present and 25% of breast cancer
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patients in addition two-thirds of cases
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are estrogen receptor and progesterone
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receptor positive a tumor that is er
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positive has a better prognosis than er
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negative her2 new cancers are generally
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highly aggressive but respond to
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targeted therapies and have good
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prognosis breast cancer usually presents
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as a breast mass or mammographic
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abnormality spread is to regional lymph
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nodes and can metastasize to the brain
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bone liver lung and ovaries
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let’s pause read and apply which lymph
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nodes are most likely affected in breast
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cancer the axillary lymph nodes are
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likely affected in metastatic disease
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for lymphatic drainage the majority of
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the breast drains to the axillary Chane
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drainage also occurs through the super
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Kovach euler nodes and internal mammary
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nodes invasive ductal carcinoma accounts
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for 80% involved breast cancers and
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neoplastic cells invade the basement
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membrane there is usually a solitary
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firm mass with poorly defined margins
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histologically is an infiltrate of
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growth invasive cells often form ducts
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or clusters pictured here they are often
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found with background DCIS which is
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circled in red 75% are er positive
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invasive lobular carcinoma counts for
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15% of all breast cancers neoplasic
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cells usually form chords or are
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arranged in a single-file orientation
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and higher power you can see the
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single-file pattern greater than 90% re
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r+ less command breast cancer types
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included inflammatory breast cancer and
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Paget disease of the nipple Paget
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disease of the nipple presents as a
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examiners patch on the nipple and is
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usually associated with underlying DCIS
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or invasive breast cancer there’s intra
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epidermal proliferation of mammary type
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carcinoma cells look at the difference
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between the area of Pageant disease
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compared to normal skin on higher power
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these cells appear as large and pale
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with a clear halo and appear differently
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than normal keratinocytes treatment of
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breast cancer often involves surgical
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management with lumpectomy versus
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mastectomy radiation to reduce local
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recurrences and chemotherapy depending
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on if there are high-risk
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characteristics of the tumor adjuvant
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hormonal therapy is typically
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recommended in ER positive tumors her
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biopsy demonstrated a low grade DCIS as
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er positive she undergoes lumpectomy and
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radiation therapy since the tumor was er
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positive she also decides to proceed
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with hormonal therapy to decrease risk
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common hormonal therapies include
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selective estrogen receptor modulators
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and aromatisse inhibitors let’s pause
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read and apply how disarms work they
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bind to estrogen receptors and exert
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tissue specific effects shown here is
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the estrogen receptor with estrogen at
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its binding site terms competitively
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bind at the receptors interestingly they
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have mixed agonist and antagonist
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activity depending on the target tissue
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for instance a common term is tamoxifen
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it has an antagonist effect in breast
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tissue making it protective against
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invasive breast cancer but has agonist
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effect on bone which makes it protective
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against bone loss an agonist activity in
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the endometrium this is why women and
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tamoxifen are at higher risk for
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development of endometrial polyps
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hyperplasia in cancer aromatase
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inhibitors are typically used in
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postmenopausal women in postmenopausal
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women most of the circulating estrogen
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is from peripheral conversion of
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androgen to estradiol by the enzyme
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aroma taste aroma taste inhibitors
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reduce circulating estradiol and
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postmenopausal women which is protective
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against breast cancer
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but associated with greater rates of
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bone loss and fractures
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this concludes the aapko basic science
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video on breast disorders we have
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covered a lot including normal breast
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anatomy and histology different types of
11:07
breast disorders and cancer and hormonal
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therapy is used in breast cancer
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[Music]
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you

Breast Disorders

Breast Development

At puberty, the female breast develops, under the influence of estrogen, progesterone, growth hormone, prolactin, insulin and probably thyroid hormone, parathyroid hormone and cortisol. This complex process typically begins between ages 8 to 14 and spans about 4 years.

The breast contains mostly fat tissue, connective tissue, and glands that following pregnancy, will produce milk. The milk is collected in the ducts and transported to 15- 25 openings that exit through the nipple.

During the menstrual cycle, the breast is smallest on days 4-7, and then begins to enlarge, under the influence of estrogen and later progesterone and prolactin. Maximum breast size occurs just prior to the onset of menses.

The breast is not round, but has a “tail” of breast tissue extending up into the axilla (or armpit). This is clinically significant because abnormalities can arise there just as they can in other areas of the breast.

Breasts are never identical, comparing right to left. One is invariably a little larger, slightly different in shape, and located differently on the chest wall. The nipples are likewise never identical but show minor differences in size, location and orientation.

The breast is divided into quadrants to better describe and compare clinical findings. The upper outer quadrant is the area of greatest mass of breast tissue. It’s also the area in which about half of all breast cancers will develop.

Adolescent Breast Problems

During adolescence, several breast growth patterns can be troubling to the adolescent and her family. Among these are:

• • Unusually early breast development
  • Unusually delayed breast development
  • Unusually large breasts (Mammary hypertrophy)
  • Unusually small breasts
  • Asymmetrical breast growth
  • Breast lumps

Initial breast development occurs on average at age 9, with the appearance of a breast bud. The normal range for breast bud appearance is from ages 8 to 13. It is common for one bud to appear up to 6 months prior to the second bud appearing.

Breast growth is then progressive, with enlargement of the breast tissue, areala and papillae, and change in shape and contour. By age 18 breast development is usually complete.

Premature thelarche is breast development prior to the age of 8 in the absence of pubic hair development. We evaluate these children to rule out estrogen-producing ovarian tumors, ingestion of estrogen-containing compounds, and the rare, true precocious puberty.

Delayed thelarche reflects absence of any breast development by age 13.

Asymmetrical breast growth during adolescence is the rule rather than the exception. Reassure the patient that the asymmetry usually evens out by the time of full maturation. Even at maturity, breasts are rarely 100% symmetrical, so minor degrees of asymmetry are expected. Because the breasts are continuing to grow and change, we usually delay any surgical intervention for asymmetric breasts until after age 18.

Mammary hypertrophy can be a distressing symptom. Because growth and development continues for a long time, if we are contemplating surgical intervention, we generally delay this surgery until the breasts are fully mature.

Breast masses in adolescents are essentially 100% benign. Because of this, surgery (excisional biopsy or fine needle aspiration) is almost never warranted.

Further, the surgical disruption of architecture can be disfiguring as the breast continues to mature.

Supernumerary breasts

Supernumerary breasts are relatively common. They are found along the “milk line,” extending from the axilla to the groin.

Most of them are not noticed clinically until pregnancy occurs. Then, under the influence of the pregnancy hormones, the breasts enlarge in preparation for lactation. It is at this time that soft swellings along the milk line occur, representing supernumerary breasts. During lactation, the extra breasts may produce milk.

These are not dangerous and are generally ignored. If they prove to be a cosmetic problem, they can be removed surgically.

More common than supernumerary breasts are supernumerary nipples. Like extra breasts, these are located in the milk line and are not dangerous.

Unless they are large, they are usually not noticed until a pregnancy. At that time, like the normal nipples, they enlarge and darken.

Inverted Nipples

Usually nipples point outward. Sometimes, they invert. When they persistently point inwards, they are called inverted nipples. This can be unilateral or bilateral.

With stimulation and nipple erection, most inverted nipples will evert. Occasionally, they remain inverted despite all efforts to evert them.

Other than for cosmetics, nipple inversion is not usually a problem. For breast-feeding, most inverted nipples will evert. Even those that do not evert may still function normally enough to allow for satisfactory infant nursing.

Non-cyclic Breast Pain

Among the common causes of non-cyclic breast pain are trauma, infection, and chest wall pain underlying the breast tissue (muscle strain or overuse of the pectoralis major muscle). Breast cancer rarely causes breast pain in the early stages and is not usually suspected unless the symptoms persist. Hormonal causes include functional ovarian cysts and pregnancy.

Women complaining of non-cyclic breast pain should have a careful examination. Common areas of tenderness include the pectoralis muscle distribution over the anterior chest wall. In this case, the muscle itself will be sore and the breast, if palpated with two hands and not pressed against the tender muscle, will be non-tender. Pain or soreness in the pectoralis major muscle is frequently found among women who have recently engaged in strenuous physical activity, and it represents a muscle strain. Chest wall pain does not involve the nipple or areola, while cyclic breast tenderness usually does. Treatment is symptomatic, with rest, some stretching exercises, and non-steroidal anti-inflammatory medication such as ibuprofen or naproxen.

A second common area for chest wall pain is along the costal margin. Direct pressure on the costochondral cartilage, without compressing breast tissue, will duplicate the pain. Compressing the chest wall with your hands placed laterally to the breasts will also duplicate the pain. This costochondritis has similar etiologies to the pectoralis major muscle tenderness, and the treatment is the same. and if the pain persists, referral will likely be necessary.

Trauma can include vigorous coughing or vomiting. The resulting strong, sustained contractions of the intercostal muscles can lead to chest wall tenderness that may be perceived by the patient as breast pain.

Cyclic Breast Pain

During the days leading up to the menstrual flow, the breasts normally are somewhat engorged and may be somewhat tender. Following the onset of menstrual flow, these changes spontaneously resolve. If the tenderness is more than mild or is clinically bothersome, it is called cyclic breast pain or mastodynia.

If examined during this time, these women also often have significantly enhanced nodularity of the breast tissue. The combination of cyclic breast pain and symmetrically thickened nodularity of the breast tissue is often called fibrocystic disease (misnamed because it’s not really a disease) or fibrocystic breast changes.

While not dangerous, women with cyclic mastodynia find it annoying and in its most severe form, interferes with some normal activities.

Some women find that by reducing or eliminating their intake of caffeine (coffee, tea, cola drinks) and taking Vitamin E supplements (400 IU daily) has seemed to improve their symptoms. Whether such improvement is pharmacologic or placebo in nature is still under debate.

Any pharmacologic approach that suppresses ovulation will be very helpful in treating cyclic mastodynia. Among these, birth control pills are the simplest. Taking BCPs in the usual fashion generally improves the pain significantly. For those who still experience significant pain, continuous birth control pills will usually suppress the pain completely.

Also effective, by virtue of ovulation inhibition, are depot medroxyprogesterone acetate, Lupron, or Danocrine, the latter two usually justified only in severe cases due to their significant side effects.

Nipple Discharge

Normally, if the ducts are stripped toward the nipple, a drop or two of clear, milky, or greenish-tinged liquid will appear. This is not considered nipple discharge.This image demonstrates milk from a lactating woman. This is also considered normal.

If the nipples spontaneously leak discharge, staining the clothing, that is not normal, nor is it normal to have bloody nipple secretions.

Nipple discharge from both breasts indicates “galactorrhea.” While a few post partum women will continue to leak small amounts of milk for years following delivery, galactorrhea in general indicates the need for a serum prolactin measurement and possibly an MRI of the pituitary gland to look for prolactin- secreting pituitary adenomas. Hypothyroidism can also cause this problem, although it is rare.

Athletes may experience small amounts of galactorrhea from constant rubbing of the nipples against clothing.

Frequent sexual stimulation of the breasts may have similar effects. The serum prolactin measurement is best made after a few days of non-stimulation of the breast. Even after a breast exam, it is often helpful to wait 2 days before measuring the serum prolactin.

Persistent discharge from a single duct, particularly if bloody, rust-colored or multicolored, suggests the presence of an intraductal lesion, such as an intraductal papilloma. While these are often benign, they need further exploration with a general or breast surgeon.

Paget’s Disease

This crusty, flaking lesion is associated with an underlying breast malignancy, invasive or in-situ. The appearance may be suggestive of Paget’s disease, but the diagnosis is generally confirmed by nipple biopsy.

The onset of the lesion is often so gradual that by the time it comes to the attention of the physician, many months or years have passed since its’ onset.

Treatment depends on the character and extent of the underlying lesion.

Breast Lump

If a dominant mass is found in the breast which persists through the menstrual cycle, it is usually biopsied, either through fine needle aspiration or excisional biopsy, depending on the clinical circumstances.

Suspicious masses (large, irregular, hard, fixed in place, with redness and dimpling of the overlying skin and nipple retraction) are usually biopsied right away.

Most masses are benign, but for those found to be malignant, earlier intervention is thought by many to lead to improved chances of successful treatment.

Breast Cyst

Breast cysts present as smooth, non-tender masses. They will often disappear over the course of the menstrual cycle, but those that persist will need further evaluation.

Cyst aspiration is frequently attempted, using a small needle and syringe.

Aspiration of the cyst fluid is performed primarily to confirm the fact of the cyst and to decompress it.

Many physicians discard the cyst fluid unless it is bloody as cyst fluid cytologic examination is felt to be of little value.

Following decompression of the cyst, the patient returns for periodic follow-up to look for recurrence. Recurrent cysts in the same location are often subjected to excisional biopsy or fine needle aspiration biopsy.

Fat Necrosis

Fat necrosis presents as a breast mass with surrounding ecchymosis (bruise). It may be tender and a history of breast trauma is identified in half the cases. Even when significant trauma is not identified, it is felt to be the general cause of this condition.

This benign condition is self-resolving, but is of clinical importance because it mimics the dominant mass found in breast cancer.

Those cases with the typical presentation can be followed to make sure they completely resolve. Those cases that are not typical or if there is any doubt, can have a fine needle aspiration to confirm the diagnosis.

Fibroadenoma

These common, benign, solid, round or oval breast tumors are most common among women ages 15-35. They are rubbery in consistency, mobile and non-tender. They rarely grow larger than 2-3 cm.

The diagnosis is usually suspected on physical exam and confirmed with fine needle aspiration or excisional biopsy. When found in teenagers, they are often simply watched because of the very low risk of malignancy compared to the architectural disturbance caused by excisional biopsy.

Breast Cancer

Breast cancer is a relatively common cancer, representing about 30% of all cancers in women. In broad terms, treatment is successful in about 3 out of 4 patients in controlling or eliminating the cancer. In about one out of four, the cancer proves fatal.

The risk of developing breast cancer increases steadily with increasing age. It is rare among women under age 25 but affects nearly one in nine of those women reaching age 90.

Breast Cancer Detection Strategies

A number of factors are associated with an increased of developing breast cancer, including:

• • Strong family history of breast cancer
  • Menopause after age 55
  • No term pregnancy prior to age 35

Despite the increased risk, most (about 80%) of breast cancer occurs in women not at increased risk for developing breast cancer. For that reason, efforts at early detection are not focused just on those with somewhat increased risks, but on all women. The primary strategy involves a three-armed effort: Periodic (annual) professional breast examination, monthly self- breast examination, and mammography at appropriate intervals.

The underlying assumption of all breast screening programs is that if we can detect a breast malignancy when it is very small, then the outcome will be better for the patient than if we discover the problem when it is bigger. Just how true that assumption is and the exact parameters of that truth are still under debate, as is the effectiveness of any of the breast cancer screening programs in improving outcome for women with breast cancer.

Breast Examination

Once a year, a woman’s breasts should be evaluated by a qualified health professional. Any significant abnormalities in texture, contour, skin, any palpable masses, retractions, dimpling or nipple discharge will require followup appropriate for the abnormality.

Professional breast exams are felt to be about 80% reliable in detecting significant breast abnormalities.

Self Breast Examination

Once a month, a woman should examine her own breasts, looking for changes in appearance, texture, or nipple discharge that was not previously present.

Examination technique is not obvious, but is a skill to be learned (and taught). Any new findings should be promptly reported to the woman’s physician or other qualified healthcare provider. Most breast cancers are first noted by the patient herself.

Some critics of self breast exams have observed that they may cause more problems than they solve. By the time a breast cancer is large enough for the woman to feel herself, it is not likely to be “early.” Further, most of the self-discovered breast lumps are benign and do not represent a threat. Nonetheless, they are often subjected to investigation, including biopsy and excision.

Mammography

The goal of mammography to to detect very early cancers or pre-cancerous changes before they have a chance to develop into a more advanced and dangerous stage. Mammography is felt to be about 80% effective in detecting significant breast abnormalities, but many of the ones that are missed by mammography can be detected by examination.

There is controversy over how frequently mammograms should be performed. If there is a clinical abnormality, mammograms can be used to gain additional information about the abnormality (a “diagnostic” mammogram). Many physicians recommend that “screening:” mammograms be performed every other year between ages 40 and 50, and annually thereafter. Some physicians dispute the usefulness of mammograms prior to age 50. Some physicians recommend mammograms more often if there is a strong family history of breast cancer. Some physicians dispute the value of screening mammograms after age 75 or 80. Some physicians dispute the value of screening mammograms at any time.

Breast Ultrasound

Breast ultrasound is used in some countries (although not commonly in the United States) to screen for breast cancer. It has the advantage that it is relatively inexpensive, quick, painless, and uses no radiation. It is particularly good at detecting cystic masses (better than mammograms). In skilled hands, it does a fair job of detecting malignancies.

Unfortunately, it is not as good at detecting malignancies as mammograms and so it is not usually used for primary screening in the U.S. It is commonly used in the U.S., however, as an adjunctive method to evaluate abnormalities palpated by the examiner or identified on mammograms.

Thermography

Thermography is a means of looking at the breast with an infrared (heat-sensitive) imaging device. It relies on the principle that cancers have increased metabolic activity, generating more heat, that can be detected with a thermographic process. While this has some theoretical advantages over other imaging techniques, in practice, thermography has not been demonstrated to be effective in early detection of significant lesions, and so is not generally used as a primary screening technique.

MRI

Magnetic Resonance Imaging is sometimes used in the diagnosis and management of breast cancer.

• • It changes the surgical management in as many as 1 in 4 patients if performed pre-operatively.
  • In high risk patients (those with a lifetime risk of greater than 20%), it seems to have greater sensitivity at detection of malignancies not found on routine mammograms, breast ultrasound, or professional breast

Unfortunately, MRI’s are significantly more expensive than other methods of detection, limiting their use for screening in the general population.

Dr. Hughey