healthcare lecture ppt

1. Treatment of Advanced Stage
(Metastatic) Breast Cancer
By. Dr. B Laxmikant Sahoo
Surgery PG

2. Breast Cancer: Statistics
 According to an article publised in
scientific reports.
 Breast cancer is the most prevalent
type of cancer among females in
many countries in the past few years.
 An estimated 22,61,419 new cases
were diagnosed in women across the
world in 2020.

3.  the 5-year survival rate of women with this
disease is 99%. If the invasive breast cancer
is located only in the breast.
 If the cancer has spread to the regional
lymph nodes, the 5-year survival rate is 86%.
 Where as If the cancer has spread to a
distant part of the body, the 5-year survival
rate is 29%.
 Breast cancer is the second most common
cause of death from cancer in women in the
developed countries after lung cancer.
 Bone is the most common site of metastasis
for breast cancer (65.1%, including single
and multiple metastatic sites), followed by
lung (31.4%), liver (26.0%) and brain (8.8%)
metastasis.

4. Aetiological factors
 Carcinoma of the breast is extremely rare before the
age of 20 years.
 Most breast cancers are diagnosed after age of 50.
 Breast cancer occurs more commonly in women with a
family history of breast cancer than in the general
population.
 There is some evidence that there is a link with diets
low in phytoestrogens.
 Alcohol consumption is associated with an increased
risk.
 Breast cancer is more common in nulliparous women
and In postmenopausal women.
 Breast cancer is more common in the obese.
 Having a first child at an early age and breast-feeding in
particular appears to be protective against breast
cancer.

5. Pathology
 Breast carcinoma is usually classifed
primarily by its histological
appearance. There are two main
types/stages of breast cancer :
 1. The tumor is limited by the
basement membrane of terminal duct-
lobular unit (TDLU) (in situ carcinoma)
and or
 2. The tumor has invaded the stroma
and reached beyond the basement
membrane of TDLU to become
invasive carcinoma.

6. The spread of breast cancer
 Local spread - The tumour increases in size and
invades other portions of the breast. It tends to involve
the skin and to penetrate the pectoral muscles and
even the chest wall if diagnosed late.
 Lymphatic metastasis - Lymphatic metastasis occurs
primarily to the axillary and the internal mammary lymph
nodes. Tumours in the posterior one-third of the breast
are more likely to drain to the internal mammary nodes.
Involvement of supraclavicular nodes and of any
contralateral lymph nodes represents advanced
disease.
 Spread by the bloodstream - It is by this route that
skeletal metastases occur, although the initial spread
may be via the lymphatic system. In order of frequency
the lumbar vertebrae, femur, thoracic vertebrae, rib and
skull are affected and these deposits are generally
osteolytic. Metastases may also commonly occur in the
liver, lungs and brain and, occasionally, the adrenal
glands and ovaries.

7. Clinical presentation
 Breast cancer is found most frequently in the
upper outer quadrant but can be found in any
portion of the breast, including the axillary
tail.
 It commonly present as a hard lump, which
may be associated with indrawing of the
nipple or overlying skin. As the disease
advances locally there may be skin
involvement with peau d’orange or frank
ulceration and fixation to the chest wall.
 This is described as cancer-en-cuirasse
when the disease progresses around the
chest wall.

9. Investigations
 Mammography – though it is an
important screening tool but a normal
mammogram does not exclude the
presence of carcinoma.
 Ultrasound – it is particularly useful in
young women with dense breasts in
whom mammograms are difficult to
interpret, and in distinguishing cysts from
solid lesions. It can also be used to
localise impalpable areas of breast. It is
not useful as a screening tool and

11. Magnetic resonance imaging
 Used to distinguish scar from recurrence in
women who have had previous breast
conservation therapy for cancer(although it is
less accurate within 9 months of radiotherapy
because of abnormal enhancement)
 to assess multifocality and multicentricity in
lobular cancer and to assess the extent of
high-grade ductal carcinoma in situ (DCIS). It
is less useful in low-grade DCIS.
 it is the best imaging modality for the breasts
of women with implants.
 as a screening tool in high-risk women
(because of family history).

12. Needle biopsy/cytology
 Fine-needle aspiration cytology (FNAC) is the
least invasive technique of obtaining a cellular
diagnosis and is rapid and very accurate if both
operator and cytologist are experienced but
invasive cancer cannot be distinguished from in
situ disease.
 Large-needle biopsy with vacuum systems – can
be used for the management of
microcalcifications or in the complete excision of
benign lesions such as fibroadenomas.
 Though a histological specimen taken by core
biopsy allows a definitive preoperative diagnosis,
differentiates between DCIS and invasive
disease and also allows the tumour to be stained
for receptor status.

13. Positron emission
tomography
 PET scan are used as a staging
investigation in patients with
T3,T4,N2,N3 breast cancer and in
patients with T1 ,T2,N0,N1 breast
cancer in presence of symptoms/signs
suggestive of metastasis.
 Inflammatory lesion (namely,
mediastinal lymphadenopathy and
pleuropulmonary lesions due to
pulmonary tuerculosis) may give false
–positive results.

14. Triple assessment
 In any patient who presents with a breast lump or
other symptoms suspicious of carcinoma, the
diagnosis should be made by a combination of
clinical assessment, radiological imaging and a
tissue sample taken for either cytological or
histological analysis, the so-called triple
assessment.

15. How is the stage determined?
 Staging systems, 7 key pieces of information
are used:
 The extent (size) of the tumor (T): How large is the
cancer? Has it grown into nearby areas?
 The spread to nearby lymph nodes (N): Has the
cancer spread to nearby lymph nodes? If so, how many?
 The spread (metastasis) to distant sites (M): Has the
cancer spread to distant organs such as the lungs or
liver?
 Estrogen Receptor (ER) status: Does the cancer have
the protein called an estrogen receptor?
 Progesterone Receptor (PR) status: Does the cancer
have the protein called a progesterone receptor?
 HER2 status: Does the cancer make too much of a
protein called HER2?
 Grade of the cancer (G): How much do the cancer cells
look like normal cells?

16. Details of the TNM staging
system
 TX: Primary tumor cannot be assessed.
 T0: No evidence of primary tumor.
 Tis: Carcinoma in situ (DCIS, or Paget disease of
the breast with no associated tumor mass)
 T1 (includes T1a, T1b, and T1c): Tumor is 2 cm
(3/4 of an inch) or less across.
 T2: Tumor is more than 2 cm but not more than 5
cm (2 inches) across.
 T3: Tumor is more than 5 cm across.
 T4 (includes T4a, T4b, T4c, and T4d): Tumor of
any size growing into the chest wall or skin. This
includes inflammatory breast cancer.

17. N categories for breast cancer
 NX: Nearby lymph nodes cannot be assessed (for
example, if they were removed previously).
 N0: Cancer has not spread to nearby lymph
nodes.
 N0(i+): The area of cancer spread contains fewer
than 200 cells and is smaller than 0.2 mm. The
abbreviation "i+" means that a small number of
cancer cells (called isolated tumor cells) were seen
in routine stains or when a special type of staining
technique, called immunohistochemistry, was
used.
 N0(mol+): Cancer cells cannot be seen in
underarm lymph nodes (even using special stains),
but traces of cancer cells were detected using a
technique called RT-PCR. RT-PCR is a molecular
test that can find very small numbers of cancer
cells.

18. N2: Cancer has spread to 4 to 9 lymph
nodes under the arm, or cancer has enlarged
the internal mammary lymph nodes
 N2a: Cancer has spread to 4 to 9
lymph nodes under the arm, with at
least one area of cancer spread larger
than 2 mm.
 N2b: Cancer has spread to one or
more internal mammary lymph nodes,
causing them to become enlarged.

19. N3: Any of the following:
 N3a: either:
 Cancer has spread to 10 or more axillary lymph nodes, with at least
one area of cancer spread greater than 2 mm,
 OR
 Cancer has spread to the lymph nodes under the collarbone
(infraclavicular nodes), with at least one area of cancer spread
greater than 2 mm.
 N3b: either:
 Cancer is found in at least one axillary lymph node (with at least one
area of cancer spread greater than 2 mm) and has enlarged the
internal mammary lymph nodes,
 OR
 Cancer has spread to 4 or more axillary lymph nodes (with at least
one area of cancer spread greater than 2 mm), and to the internal
mammary lymph nodes on sentinel lymph node biopsy.
 N3c: Cancer has spread to the lymph nodes above the collarbone
(supraclavicular nodes) on the same side of the cancer with at least
one area of cancer spread greater than 2 mm.

20. M categories for breast cancer
 M0: No distant spread is found on x-rays (or other
imaging tests) or by physical exam.
 cM0(i+): Small numbers of cancer cells are
found in blood or bone marrow (found only by
special tests), or tiny areas of cancer spread (no
larger than 0.2 mm) are found in lymph nodes
away from the underarm, collarbone, or internal
mammary areas.
 M1: Cancer has spread to distant organs (most
often to the bones, lungs, brain, or liver) as seen on
imaging tests or by physical exam, and/or a biopsy
of one of these areas proves cancer has spread
and is larger than 0.2mm.

21. Staging of breast cancer
 Classical staging of breast cancer by
means of the TNM (tumour–node–
metastasis) or UICC (Union
Internationale Contre le Cancer)
criteria is used less often with
increased knowledge of the biological
variables that affect prognosis.

22. Stage 0
 Stage 0 cancers are limited to the inside of the milk
duct and are non-invasive (does not invade nearby
tissues).
 Ductal carcinoma in situ (DCIS) is a stage 0
breast tumor.
 Lobular carcinoma in situ (LCIS) used to be
categorized as stage 0, but this has been changed
because it is not cancer. Still, it does indicate a
higher risk of breast cancer.

23. In situ carcinoma
 It is a preinvasive cancer that has not breached the
epithelial basement membrane. This was previously a
rare, usually asymptomatic, finding in breast biopsy
specimens but is becoming increasingly common
because of the advent of mammographic screening;
 It may be ductal (DCIS) or lobular (LCIS).
 Although mastectomy is curative, this constitutes
overtreatment in many cases.
 Patients with a high score benefit from radiotherapy
after excision, whereas those of low grade, whose
tumour is completely excised, need no further
treatment.
 Tumours are also stained for Her-2 or c-erbB2 (a
growth factor receptor) as patients who are positive can
be treated with the monoclonal antibody trastuzumab
(Herceptin®), either in the adjuvant or relapse setting.

24. Stages I-III
 Treatment for stages I to III breast cancer usually
includes surgery and radiation therapy, often with
chemo or other drug therapies either before
(neoadjuvant) or after (adjuvant) surgery.
 Stage I: These breast cancers are still relatively small
and either have not spread to the lymph nodes or have
only a tiny area of cancer spread in the sentinel lymph
node (the first lymph node to which cancer is likely to
spread).
 Stage II: These breast cancers are larger than stage I
cancers and/or have spread to a few nearby lymph
nodes.
 Stage III: These tumors are larger or are growing into
nearby tissues (the skin over the breast or the muscle
underneath), or they have spread to many nearby
lymph nodes.

25. Treatment of cancer of the
breast
 The two basic principles of treatment are
to reduce the chance of local recurrence
and the risk of metastatic spread.
 Treatment of early breast cancer will
usually involve surgery with or without
radiotherapy.
 Systemic therapy such as chemotherapy
or hormone therapy is added if there are
adverse prognostic factors such as
lymph node involvement, indicating a
high likelihood of metastatic relapse.

26. Algorithm for management of
operable breast cancer
 Achieve local control
 Appropriate surgery
 Wide local excision (clear margins) and
radiotherapy, or Mastectomy ± radiotherapy (offer
reconstruction – immediate or delayed)
 Combined with axillary procedure
 Await final pathology and receptor measurements
 Use risk assessment tool; stage if appropriate
 Treat risk of systemic disease
 Offer chemotherapy if prognostic factors poor;
include Herceptin if Her-2 positive
 Radiotherapy
 Hormone therapy if oestrogen receptor or
progesterone receptor positive.

27. Treatment of advanced
(Metastatic) Breast Cancer
 What is advanced stage ?
 If cancers have spread
(metastasized) beyond the breast and
nearby lymph nodes to other parts of
the body stage IV.
 Treatment can often shrink tumors (or
slow their growth), improve symptoms,
and help some women live longer.
These cancers are considered
incurable.

28.  For women with stage IV breast
cancer, systemic drug therapies are
the main treatments.
 Hormone therapy
 Chemotherapy (chemo)
 Targeted drugs
 Immunotherapy
 Some combination of these
 Surgery and/or radiation therapy may
be useful in certain situations

29. RADIOTHERAPY
 Radiotherapy is shown to decrease the
risk of locoregional and systemic
recurrence and improve survival. The
indication includes the following;-
 Patients with locally advanced breast
cancers T3,T4,N1,N2,N3 disease,
 Following breast concervative surgery
 After mastectomy if tumour size >
5cm,skin or chest wall
involvement,lymphovascular invasion
present. Or axillary lymphnodes positive
for metastasis.

30. CHEMOTHERAPY
 This is the most common systemic treatment
for breast cancer.
 Regimens
 Cyclophosphamide(C) ,Methotraxate (M),and
5-fluorouracil(F) (CMF)
 Anthracycline-based regimen : CAF
(A,Adriamycin[doxorubicin]),CEF(E,epirubicin
)
 Taxane(docetaxel,paclitaxel)-based
regimens.
 Adjuvant chemotherapy is indicated for all
invasive carcinoma >1cm in
diameter,tumours >0.5 cm with poor
prognostic factors and node positive tumours.

31. Systemic (drug) treatments for
stage IV breast cancer
 Treatment often continues until the
cancer starts growing again or until
side effects become unacceptable. If
this happens, other drugs might be
tried. The types of drugs used for
stage IV breast cancer depend on the
hormone receptor status, the HER2
status of the cancer, and sometimes
gene mutations that might be found.

32. Hormone receptor-positive
cancers
 Women with hormone (estrogen or
progesterone) receptor-positive cancers are
sometimes treated first with hormone therapy
(tamoxifen or an aromatase inhibitor). This
may be combined with a targeted drug such
as a CDK4/6 inhibitor, everolimus, or a PI3K
inhibitor.
 Women who haven’t yet gone through
menopause are often treated with tamoxifen
or with medicines that keep the ovaries from
making hormones along with other drugs.

33. Hormone receptor-negative
cancers
 Chemo is the main treatment for
women with hormone (estrogen and
progesterone) receptor-negative
cancers, because hormone therapy
isn’t helpful for these cancers.

34. HER2-positive cancers
 The first therapy given is usually
chemotherapy in combination
with trastuzumab (Herceptin) and
pertuzumab (Perjeta), both HER2 targeted
drugs. If the cancer grows, other options
might include:
◦ an antibody-drug conjugate
◦ a kinase inhibitor with an anti-HER2 drug or with
a chemo drug or both
◦ other HER2 targeted drugs with chemo
 Hormone therapy might be added to these
drug combinations if the cancer is also
hormone-receptor positive.

35. HER2-low cancers
 For breast cancers that are
considered HER2-low, and have
spread to distant sites, the antibody-
drug conjugate fam-trastuzumab
deruxtecan (Enhertu) might be an
option.

36. HER2-negative cancers in
women with a BRCA gene
mutation
 These women are typically treated
with a targeted drug called a PARP
inhibitor, such as olaparib or
talazoparib. Chemotherapy drugs and
hormone drugs are also very helpful in
treating these cancers.

37. HER2-negative breast cancers
in women with a PIK3CA gene
mutation
 About 30% to 40% of metastatic ER-positive
breast cancers have a PIK3CA gene
mutation. Alpelisib is a targeted drug known
as a PIK3 inhibitor that can be used along
with the hormone drug fulvestrant to treat
postmenopausal women with advanced
hormone receptor-positive breast cancer. For
this drug to work, there must be
a PIK3CA mutation found on a biopsy done
on the tumor tissue or of the cancer cells in
the blood (liquid biopsy).

38. Triple-negative breast cancer
(TNBC)
 An immunotherapy drug along with chemotherapy might be
used in people with advanced triple-negative breast cancer
whose tumor makes the PD-L1 protein.
 For women with TNBC and a BRCA mutation, drugs called
PARP inhibitors (like olaparib or talazoparib) may be
considered.
 For breast cancers in which the cancer cells show high levels
of gene changes called microsatellite instability (MSI) or
changes in any of the mismatch repair (MMR) genes (MLH1,
MSH2, MSH6, and PMS2), immunotherapy with the drug
pembrolizumab might be used.
 Pembrolizumab might also be an option for TNBC that has
other gene or protein changes.
 For TNBC that does not have any specific gene or protein
changes, chemo alone or the antibody-drug
conjugate sacituzumab govitecan (Trodelvy) might be an
option.

39. Local or regional treatments
for stage IV breast cancer
 Although systemic drugs are the main treatment for stage IV
breast cancer, local and regional treatments such as surgery,
radiation therapy, or regional chemotherapy are sometimes
used as well. These can help treat breast cancer in a specific
part of the body, but they are very unlikely to get rid of all of
the cancer. These treatments are more likely to be used to
help prevent or treat symptoms or complications from the
cancer.
 Radiation therapy and/or surgery may also be used in certain
situations, such as:
◦ When the breast tumor is causing an open or painful wound in the
breast (or chest)
◦ To treat a small number of metastases in a certain area, such as
the brain
◦ To help prevent or treat bone fractures
◦ When a cancer is pressing on the spinal cord
◦ To treat a blood vessel blockage in the liver
◦ To provide relief of pain or other symptoms anywhere in the body

40. Advanced cancer that
progresses during treatment
 Treatment for advanced breast cancer can
often shrink the cancer or slow its
growth (sometimes for many years), but after
a time, it tends to stop working.
◦ For hormone (estrogen or progesterone)
receptor-positive cancers that were being treated
with hormone therapy, switching to another type
of hormone therapy sometimes helps.
◦ If the cancer is no longer responding to any
hormone drugs, chemotherapy immunotherapy,
or PARP inhibitors might be options depending
on specific features of the cancer or any gene
changes that might be present.

41.  HER2-positive cancers that no longer respond
to trastuzumab (Herceptin) might respond to
other drugs that target the HER2 protein.
Options for women with HER2-positive cancers
might include:
◦ Pertuzumab (Perjeta) with chemo and trastuzumab
◦ Ado-trastuzumab emtansine (Kadcyla)
◦ Fam-trastuzumab deruxtecan (Enhertu)
◦ Margetuximab (Margenza) with chemo
◦ Lapatinib (Tykerb) and the oral chemo drug
capecitabine
◦ Lapatinib and an aromatase inhibitor (for hormone
receptor-positive cancers)
◦ Neratinib (Nerlynx) and the chemo drug
capecitabine (this combination can be helpful for
cancers that have spread to the brain)
◦ Tucatinib (Tukysa), trastuzumab, and the chemo
drug capecitabine (this combination can be helpful
for cancers that have spread to the brain)

42. References
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of the Breast. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper
JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.
 Jagsi R, King TA, Lehman C, Morrow M, Harris JR, Burstein HJ. Chapter 79:
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Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and
Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins;
2019.
 National Cancer Institute. Physician Data Query (PDQ). Breast Cancer Treatment
– Health Professional Version. 2021. Accessed at
https://www.cancer.gov/types/breast/hp/breast-treatment-pdq on August 30, 2021.
 National Comprehensive Cancer Network (NCCN). Practice Guidelines in
Oncology: Breast Cancer. Version 7.2021. Accessed at
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2021.