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Perjeta

Perjeta® is an FDA-approved first-line treatment for HER2-positive metastatic breast cancer, used in combination with Herceptin (trastuzumab) and docetaxel (chemotherapy). This targeted therapy blocks HER2 signaling, helping to control cancer growth, and has been shown to significantly increase the time patients live without disease progression and improve tumor shrinkage rates. The combination of Perjeta, Herceptin, and docetaxel enhances the efficacy of treatment compared to Herceptin and docetaxel alone.

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Breast Cancer Insights•
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PERJETA® is a first-line treatment for HER2positive metastatic breast cancer. • PERJETA is an FDA-approved treatment for HER2-positive metastatic breast cancer. It is a targeted therapy used as part of a first-line HER2positive metastatic breast cancer treatment plan, in combination with Herceptin (trastuzumab) and docetaxel (chemotherapy).
PERJETA is referred to as a HER2 dimerization inhibitor (HDI).
PERJETA is referred to as a HER2 dimerization inhibitor (HDI). • Learn more about HDIs.
HER family receptors are activated by ligand-induced dimerization, or receptor pairing.3 Dimerization is a critical step in HER family-mediated signaling, and HER receptors are able to homodimerize or heterodimerize with
What is HER2-positive breast cancer? All cells have HER2 receptors, including healthy cells and cancer cells. In HER2-positive breast cancer, tumor cells have more HER2 receptors than normal. Too much HER2 makes these cancer cells grow and divide too rapidly. NONCANCEROUS CELL
What is HER2-positive breast cancer? All cells have HER2 receptors, including healthy cells and cancer cells. In HER2-positive breast cancer, tumor cells have more HER2 receptors than normal. Too much HER2 makes these cancer cells grow and divide too rapidly. HER2-POSITIVE CANCER CELL Cancer treatments called HER2-targeted therapies have been developed to target the HER2 receptor. PERJETA is one of those HER2-targeted therapies.
PERJETA is a targeted therapy for treating HER2-positive metastatic breast cancer. PERJETA was designed to search for and attack cancer cells with too much HER2 HER2 tells cancer cells to grow by sending signals HER2 works by sending signals that tell cells to grow and divide One way that HER2 can send signals is by pairing with other HER receptors. This process is called dimerization
PERJETA is a targeted therapy for treating HER2-positive metastatic breast cancer. PERJETA works with Herceptin to target HER2 PERJETA and Herceptin both target HER2 but work in different ways PERJETA is thought to block one method of signaling so that certain receptors are unable to pair (dimerization) with HER2 Together, PERJETA and Herceptin are thought to create a stronger blockade against HER2 signals, helping to slow down cancer cell growth HER2 signaling could inhibit the growth of tumors.
PERJETA is proven to help control cancer growth Adding PERJETA to Herceptin and docetaxel (chemotherapy) increased the time people lived without their cancer growing or spreading by an average of 50%, compared with people who took Herceptin and docetaxel (chemotherapy) alone
ERJETA helped people live longer On average, people who were given PERJETA, Herceptin, and docetaxel (chemotherapy) lived significantly longer than people given only Herceptin and docetaxel (chemotherapy) PERJETA is proven to shrink tumors 80% of people taking the PERJETA combination had their tumors shrink, compared to 69% of people taking Herceptin and docetaxel (chemotherapy) alonePeople who had their tumors shrink maintained this response, on average, for 62% longer on the PERJETA combination compared with people taking only Herceptin and docetaxel (chemotherapy) (20.2 months vs 12.5 months) PERJETA is taken together with Herceptin, another HER2 therapy PERJETA is a targeted therapy used as part of a first-line HER2-positive metastatic breast cancer treatment plan. This treatment plan includes Herceptin and docetaxel, a type of chemotherapy. PERJETA and Herceptin both target HER2 but are believed to work in complementary ways. The combination may increase death of cancer cells.
THE BREAST
I. Introduction/General Information A. Embryologically: belong to integument B. Functionally: part of reproductive system 1. Respond to sexual stimulation 2. Feed babies
Breast, continued … C. Modified apocrine sweat glands - apex of cell becomes part of secretion and breaks off D. Present in males and females
II. Anatomy A. Position and Attachment 1. Lateral aspect of pectoral region 2. 3. 4. 5. Located between ribs 3 and 6/7 Extend form sternum to axilla Surrounded by superficial fascia Rest on deep fascia
Breast Anatomy
Position & attachment, continued …. 6. Fixed to skin & underlying fascia by fibrous C.T. bands a. Cooper’s (Suspensory) Ligaments b. Ligaments may retract when breast tumors are present
Cooper’s Suspensory Ligaments
Position & attachment, continued … 6. Left breast is usually slightly larger 7. Base is circular, either flattened or concave 8. Separated from pectoralis major muscle by fascia, retromammary space
Retromammary Space Retromammary Space
Anatomy, continued … B. Structure 1. Outer surface convex, skin covered 2. Nipple: a. At fourth intercostal space b. Small conical/cylindrical prominence below center
Nipple location 4th intercostal space
Structure, continued … c. Surrounded by areola: pigmented ring of skin d. Thin skinned region lacking hair, sweat glands e. Contains areolar glands
Structure, continued … 3. Areola: contains dark pigment that intensifies with pregnancy a. Circular and radial smooth muscle fibers b. Cause nipple erection
Areola
Structure, continued … 4. Each breast consists of ~ 20 lobes of secretory tissue a. Each lobe has one lactiferous duct b. Lobes (and ducts) arranged radially c. Embedded in connective tissue & adipose of superficial fascia d. Lobes composed of lobules e. Lobules comprise alveoli
Lobes and Lobules
Structure, continued … 5. Excretory (lactiferous) ducts converge toward areola a. Form ampullae (collection sites of lactiferous sinuses) b. Ducts become contracted at base of nipple
Excretory (lactiferous) ducts
Structure, continued … 6. Secretory epithelium a. Changes with hormonal signals b. Onset of menstruation c. Pregnancy (glands begin to enlarge at 2nd month) d. After birth, 1st secretion is colostrom (contain antibodies)
Structure, continued … 7. “Tail of Spence” = axillary tail a. prolongation of upper, outer quadrant in axillary direction b. Passes under axillary fascia c. May be mistaken for axillary lymph nodes
“Tail of Spence” Axillary Tail
Structure, continued … 8. Fatty Tissue: surrounds surface, fills spaces between lobes a. Determines form & size of breast b. No fatty deposit under nipple & areola
Breast: Fatty Tissue
Structure, continued … C. Vessels & nerves 1. Arteries: derived from thoracic branches of three pairs of arteries a. Axillary arteries 1) continuous with subclavian a. 2) gives rise to external mammary ( = lateral thoracic) artery
Vessels & Nerves, continued … b. Internal mammary (thoracic) arteries 1) first descending branch of subclavian artery 2) supply intercostal spaces & breast 3) used for coronary bypass surgery c. Intercostal arteries: 1) numerous branches from internal & external mammary arteries 2) supply intercostal spaces & breast
Arterial Supply to the Breast Subclavian a. Axillary a. External mammary (thoracic) a. Internal mammary (thoracic) a.
Vessels & Nerves, continued … 2. Veins: a. form a ring around the base of the venosus”) nipple (“circulus b. Large veins pass from circulus venosus to circumference of mammary gland, then to c. External mammary v to axillary v or d. Internal mammary v to subclavian v
Veins draining the Breast Subclavian vein External mammary vein
Breast Anatomy, con’t… 3. Innervation: derived from: a. anterior & lateral cutaneous nerves of thorax b. spinal segments T3 – T6
Structure, continued … 4. Lymphatics: clinically significant! a. Glandular lymphatics drain into anterior axillary (pectoral) nodes  central axillary nodes  apical nodes  deep cervical nodes  subclavicular (subclavian) nodes b. Medial quadrants drain into parasternal nodes
Lymph Nodes of the Breast Subclavian nodes Axillary nodes Lateral pectoral nodes Parasternal nodes
Lymphatics, continued … c. Superficial regions of skin, areola, nipples: -form large channels & drain into pectoral nodes d. NOTE: axillary nodes also drain lymph from arm
Lymph Nodes and Lymph Drainage Axillary Nodes
Routes of Metastasis • From medial lymphatics to parasternal nodes – Then to mediastinal nodes • Across the sternum in lymphatics to opposite side via cross-mammary pathways – Then to contralateral breast • From subdiaphragmatic lymphatics to nodes in abdomen – Then to liver, ovaries, peritoneum
Major Routes of Metastasis Channels to Contralateral Breast Axillary Lymph Channels Subdiaphragmatic Lymph Channels
Structure, continued … D. Anomalies 1. Inverted nipple: congenital or due to cancer 2. Ectopic nipple: a. “polythelia” or “hyperthelia” b. additional nipples along milk line 3. Amastia 4. Micromastia
Anomalies, continued … 5. Macromastia 6. Gynecomastia a. breast development of male in areolar region b. noted in males who smoke marijuana at puberty
III. Diseases of the Breast A. Most are readily detectable B. Etiology unknown, influencing factors 1. Sex 2. Heredity
Diseases of the breast, continued … 3. Endocrine influence a. Menstruation – tenderness from fluid engorgement b. Post-menopause 1) decrease of fibro-cystic disease 2) increase in cancer c. Pregnancy
Diseases of the Breast, continued … C. General symptoms & signs 1. Nipple discharge a. always significant if not pregnant. b. May be due to benign pituitary tumor. 2. Local pain, tenderness 3. Duration of lesion 4. Size, rate of growth
Symptoms & Signs, continued … 5. Retraction sign: “dimpling” involving skin, nipple or areola 6. Mobility of mass a. Benign = movable 1) not attached 2) not invasive b. Malignant = attached 1)May grow into bone
Symptoms & Signs, continued … 7. Consistency of mass a. Cysts = fluctuant; compressible b. Fibroadenoma = rubbery c. Carcinoma = firm, hard (like gravel) 8. Axillary area lymph node enlargement
D. Benign breast conditions 1. Infection = usually during or after lactation a. Recurrent, subareolar abscess b. TB of the breast 2. Trauma = contusion 3. Hypertrophy = seen in either sex at adolescence a. Gynecomastia = in males
Hypertrophy, continued … b. Other causes 1) testicular or pituitary tumor 2) cirrhosis 3) hypogonadism = not enough testosterone 4) estrogen administration for prostate cancer
Breast Cancer
Breast cancer originates in breast tissue and arises from the ductal tissue of the breast and, less commonly, the lobulartissue. There are several forms of breast cancer based, in part, on cellular and genetic characteristics,
Types of Breast Cancer
HER2-Positive Overabundance of the HER2 protein classifies the breast cancer as HER2positive and causes breast cancer cells to multiply, spread more rapidly, and survive longer than other breast cancers
Ductal Carcinoma in situ (DCIS) Ductal cancer cells Carcinoma refers to any cancer that begins in the skin or other tissues that cover internal organs 63 Illustration © Mary K. Bryson Normal ductal cell
Hormone Receptor-Positive Breast cancer cells that express hormone receptors for estrogen (ER) and/or progesterone (PR) are dependent on the signaling of those receptors
Invasive Ductal Carcinoma (IDC – 80% of breast cancer) Ductal cancer cells breaking through the wall • The cancer has spread to the surrounding tissues 65 Illustration © Mary K. Bryson
67 Illustration © Mary K. Bryson Range of Ductal Carcinoma in situ
Invasive Lobular Carcinoma (ILC) Lobular cancer cells breaking through the wall 68 Illustration © Mary K. Bryson
Cancer Can also Invade Lymph or Blood Vessels Cancer cells invade lymph duct Cancer cells invade blood vessel 69 Illustration © Mary K. Bryson
Mammography • Use a low-dose x-ray system to examine breasts • Digital mammography replaces x-ray film by solid-state detectors that convert x-rays into electrical signals. These signals are used to produce images that can be displayed on a computer screen (similar to digital cameras) • Mammography can show changes in the breast up to two years before a physician can feel them 72
Computer-Aided Diagnosis • Mammography allows for efficient diagnosis of breast cancers at an earlier stage • Radiologists misdiagnose 10-30% of the malignant cases • Of the cases sent for surgical biopsy, only 10-20% are actually malignant CAD systems can assist radiologists to Reduce these problems National Cancer Institute 73
What Mammograms Show Two of the most important mammographic indicators of breat cancers – Masses – Microcalcifications: Tiny flecks of calcium – like grains of salt – in the soft tissue of the breast that can sometimes indicate an early cancer. 74
Detection of Malignant Masses Malignant masses have a more spiculated appearance benign malignant 75
Mammogram – Difficult Case • Heterogeneously dense breast • Cancer can be difficult to detect with this type of breast tissue • The fibroglandular tissue (white areas) may hide the tumor • The breasts of younger women contain more glands and ligaments resulting in dense breast tissue 76
Mammogram – Easier Case • With age, breast tissue becomes fattier and has fewer glands • Cancer is relatively easy to detect in this type of breast tissue 77
Different Views Side-to-Side MRI - Cancer can have a unique appearance – many small irregular white areas that turned out to be cancer (used for diagnosis) Top-to-Bottom 78
Benign Conditions, continued 4. Tumors & cysts a. Fibroadenoma = most common benign breast tumor
Tumors and Cysts, con’t… b. Breast Cyst 1. Benign 2. May be aspirated if large
Benign conditions, continued … c. Fibrocystic breast changes 1) 20%+ of remenopausal women 2) discomfort, cysts 3) treatment rarely required 4) More likely to not detect a developing cancer
Tumors & cysts, continued …. d. Intraductal papilloma - may produce “chocolate” or bloody discharge from nipple e. Lipoma: common - fatty tumors
Carcinoma of the breast 1. Most common malignant tumor among women 2. 1/8 of women will develop breast cancer a. 1/6 in Orange County b. 1/5 in San Francisco 3. Generally no discomfort
Progression to Breast Cancer
Carcinoma of breast, continued … 4. Physical signs: a. b. c. d. e. Slowly growing, painless mass May demonstrate retracted nipple May be bleeding from nipple May be distorted areola, or breast contour Skin dimpling in more advanced stages with retraction of Cooper’s ligaments
Physical signs, continued … f. Attachment of mass g. Edema of skin 1)with “orange skin” appearance (peau d’orange) 2) due to blocked lymphatics h. Enlarged axillary or deep cervical lymph nodes
Breast Cancer, con’t… 5. Common sites for metastasis a. Lungs & pleura b. Skeleton system (skull, vertebral column, pelvis) c. Liver 6. Atypical carcinomas a. Inflammatory carcinoma (hormonal, chemotherapy) b. Paget’s disease of the breast pagget's disease
Scalar Field • A scalar field is a n-dimensional space with a scalar value attached to each point in the space (e.g., a gray-scale image) 89
Scalar Field and Gradient • A scalar field is a n-dimensional space with a scalar value attached to each point in the space (e.g., a gray-scale image) • The derivative of a scalar field results in a vector field called the gradient – i.e., the gradient is a vector field • which points in the direction of the greatest rate of increase of the scalar field, and • whose magnitude is the greatest rate of change 90 Black representing Higher values
Gradient The derivative of a scalar field results in a vector field called the gradient – i.e., the gradient is a vector field • which points in the direction of the greatest rate of increase of the scalar field, and • whose magnitude is the greatest rate of change 91 Black representing Higher values
Cartesian Gradient  g (P ) For an image function I(P) where P is a pixel, the Cartesian gradient at P is: I ( P) 92 I ( P) y I ( P) x tan Magnitude: Orientation: arctan P x I ( P) y g ( P) ( P) (P) I ( P) y I ( P) x m( P) I ( P) x 2 I ( P) y 2 I ( P) y I ( P) x
Radial Gradient • The radial gradient vector has the same magnitude as the Cartesian gradient vector, but • the orientation is given as: r ( P) 93 ( P) ( P) Radial gradient r(P)  g (P ) (P) P (P)
Feature: Spiculation [Huo et al.] • Extract the mass using a region-growing technique • The maximum gradient and its angle relative to the radial direction are computed • Calculate the full-width at half-maximum (FWHM) from the cumulative gradient orientation histogram 94
Feature: Spiculation [Chan et al.] • Determine the outline of the segmented mass • Obtain the rubber-bandstraightening-transformed image – The spicules become approximately aligned in a similar direction • The rectangular region can then be subjected to texture analysis 95
Breast Calcifications • Calcifications show up as white spots on a mammogram • Round well-defined, larger calcifications (left column) are more likely benign • Tight cluster of tiny, irregularly shaped calcifications (right column) may indicate cancer 96
Calcification Features • The morphology of individual calcification, e.g., shape, area, and brightness • The heterogeneity of individual features characterized by the mean, the standard deviation, and the maximum value for each feature. • Cluster features such as total area, compactness 97
Database Approach to Computer-Aided Diagnosis Content-based image retrieval techniques can provide radiologists “visual aids” to increase confidence in their diagnosis • The database consists of a large number of images with verified pathology results • Diagnosis is done by submitting the suspected mass region as a query to retrieve similar cases from the database 98
A Mammography CAD System [Giger et al.] Probability of malignancy Similar images of known diagnosis Indicates the unknown lesion relative to all lesions in the database 99